CD4 but not CD8 is comodulated with the T-cell antigen receptor (TCR) after activation of a CD4+ CD8+ human leukemia line with staphylococcal enterotoxin

Intra-abdominal infections in children that follow perforation of viscus often involve the gastrointestinal aerobic and anaerobic bacterial flora. These organisms possess various virulence factors and exhibit potential synergy. The intra-abdominal infection is biphasic, with the Enterobacteriaceae as the major pathogens in the peritonitis stage, and the Bacteroides fragilis group predominating in the abscess stage. Experiments with animals and experience in patients support the need to use single or combined antimicrobial agent therapy that is effective against both Enterobacteriaceae and the B. fragilis group.     

CD8-deficient mice exhibit augmented mucosal immune responses and intact adjuvant effects to cholera toxin

We used normal, CD4 and CD8 gene-targeted mice to investigate the role of CD4+ and CD8+ T cells in the regulation of gut mucosal immune responses following oral immunizations with cholera toxin (CT) adjuvant. Phenotypic analysis of mucosa-associated tissues revealed normal CD3+ T-cell frequencies in CD4-/- and CD8-/- mice such that in CD4-/- mice the CD8+ and double-negative (DN) T cells were increased. In CD8-/- mice the CD4+ T cells were increased, with the exception that in the intraepithelial compartment the CD3+ T cells were predominantly DN gamma delta T-cell receptor (TCR)+ T cells. All mice, normal and deficient, failed to respond to oral immunization with the antigen, keyhole limpet haemocyanin (KLH), alone. In the presence of CT adjuvant, however, CD8-/- mice consistently exhibited three- to fivefold stronger gut mucosal responses compared to normal C57B1/6 mice. By contrast, no difference was observed for systemic responses between CD8-/- and normal mice. Thus the up-regulation selectively affected mucosal responses, suggesting that, contrary to the CD8-/- mouse gut, the normal gut mucosa may host CD8+ T cells that exert a local suppressive effect on T- and B-cell responses. The magnitude of the enhancing effect of CT was comparable in CD8-/- and normal mice, clearly demonstrating that the adjuvant mechanism of CT does not require CD8+ T cells. On the other hand, the adjuvant effect of CT required CD4+ T cells, because no or poor anti-KLH responses were observed in CD4-/- mice. In both normal and CD8-/- mice CT adjuvant promoted KLH-specific CD4+ T-cell printing without any selective effect on the differentiation towards a T-helper type-1 (Th1) or Th2 dominance. Furthermore, CT adjuvant increased the frequency of CD4+ T cells expressing a memory phenotype, i.e. CD44high, LECAM-1low and CD45RBlow. We have shown, using gene-targeted mice, that CD8+ T cells are not required for the adjuvant effect of CT, and that CD8+ T cells may exert local mucosal down-regulation of intestinal immune responses.     

Identification of Trypanosoma cruzi trans-sialidase family members as targets of protective CD8+ TC1 responses

CD8+ T lymphocytes play a critical role in immunity to Trypanosoma cruzi. However, the target molecules of this T cell subset have not been elucidated. In this work, we report the identification of an H-2Kb-restricted CTL epitope within two trypomastigote surface Ags encoded by members of the T. cruzi sialidase/trans-sialidase gene superfamily. Octapeptide VDYNFTIV sensitized target cells for lysis by CD8+ CTL generated from spleens of T. cruzi-infected mice. Peptide-specific CD8+ T cell lines were cytotoxic, secreted IFN-gamma and TNF-alpha, but low to undetectable levels of IL-4 and IL-5, and were able, upon adoptive transfer, to confer a high degree of protection against challenge infection. Finally, the protective determinant appears to be conserved among parasites from diverse geographic locations. This constitutes the first identified class I MHC-restricted epitope in T. cruzi and provides the basis for the search of additional targets to be considered in the development of vaccines against Chagas' disease.     

Comparison of the abilities of different attenuated Salmonella typhimurium strains to elicit humoral immune responses against a heterologous antigen

We compared the abilities of different Salmonella enterica var. Typhimurium (S. typhimurium) strains harboring mutations in the genes aroA, aroAD, purA, ompR, htrA, and cya crp to present the heterologous antigen, C fragment of tetanus toxin, to the mouse immune system. Plasmid pTETtac4, encoding C fragment, was transferred into the various S. typhimurium mutants, and the levels of antigen expression were found to be equivalent. After primary oral immunization of BALB/c mice, all attenuated strains were capable of penetrating the gut epithelium and colonizing the Peyer's patches and spleens of mice. Of all strains compared, the delta purA mutant colonized and persisted in the Peyer's patches at the lowest level, whereas the delta htrA mutant colonized and persisted in the spleen at the lowest level. The level of specific antibody elicited by the different strains against either S. typhimurium lipopolysaccharide or tetanus toxoid was strain dependent and did not directly correlate to the mutants' ability to colonize the spleen. The level of immunoglobulin G1 (IgG1) and IgG2a antibody specific for tetanus toxoid was determined in mice immunized with four S. typhimurium mutants. The level of antigen-specific IgG1 and IgG2a was significantly lower in animals immunized with S. typhimurium delta purA. Antigen-specific T-cell proliferation assays indicated a degree of variability in the capacity of some strains to elicit T cells to the heterologous antigen. Cytokine profiles (gamma interferon and interleukin-5) revealed that the four S. typhimurium mutants tested induced a Th1-type immune response. Mice were challenged with a lethal dose of tetanus toxin 96 days after oral immunization. With the exception of the S. typhimurium delta purA mutant, all strains elicited a protective immune response. These data indicate that the level of total Ig specific for the carried antigen, C fragment, does not correlate with the relative invasiveness of the vector, but it is determined by the carrier mutation and the background of the S. typhimurium strain.     

Rapid induction of primary human CD4+ and CD8+ T cell responses against cancer-associated MUC1 peptide epitopes

Antigen-specific MHC class II- and class I-restricted helper and cytotoxic T cell responses are important anti-cancer immune responses. MUC1 mucin is a potentially important target for immunotherapy because of its high expression on most human adenocarcinomas. MUC1 peptide-specific type 1 T cell responses were generated in vitro using human peripheral blood lymphocytes (PBL), incubated with liposomes containing synthetic MUC1 lipopeptide antigen. Only two weekly stimulations with the liposomal MUC1 formulation led to the generation of potent anti-MUC1-specific T cell proliferation as well as class I-restricted cytotoxic responses. Thus the use of PBL pulsed with liposome-encapsulated antigen provides an effective approach of rapidly generating effective antigen-presenting cell (APC) function as well as antigen specific T cells in vitro. It may be feasible to use this technology for the rapid and effective generation of APC and/or T cells as cellular vaccines for adenocarcinomas.     

CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice

Successful neonatal immunization of humans has proven difficult. We have evaluated CpG-containing oligonucleotides as an adjuvant for immunization of young mice (1-14 days old) against hepatitis B virus surface antigen. The protein-alum-CpG formulation, like the DNA vaccine, produced seroconversion of the majority of mice immunized at 3 or 7 days of age, compared with 0-10% with the protein-alum or protein-CpG formulations. All animals, from neonates to adults, immunized with the protein-alum vaccine exhibited strong T helper (Th)2-like responses [predominantly IgG1, weak or absent cytotoxic T lymphocytes (CTL)]. Th2-type responses also were induced in young mice with protein-CpG (in 1-, 3-, and 7-day-old mice) and protein-alum-CpG (in 1- and 3-day-old mice) but immunization carried out at older ages gave mixed Th1/Th2 (Th0) responses. DNA vaccines gave Th0-like responses when administered at 1 and 7 days of age and Th1-like (predominantly IgG2a and CTL) responses with 14-day-old or adult mice. Surprisingly, the protein-alum-CpG formulation was better than the DNA vaccine for percentage of seroconversion, speed of appearance, and peak titer of the antibody response, as well as prevalence and strength of CTL. These findings may have important implications for immunization of human infants.     

Specific suppression of human CD4+ Th cell responses to pig MHC antigens by CD8+CD28- regulatory T cells

Evidence that T cells can down-regulate the immune response by producing or consuming certain cytokines or by lysing APCs or Th cells has been provided in various systems. However, the generation and characterization of suppressor T cell lines have met with limited success. Here we show that xenospecific suppressor T cells can be generated by in vitro stimulation of human T cells with pig APCs. Similar to allospecific suppressors, these xenospecific suppressor T cells carry the CD8+CD28- phenotype and react to MHC class I Ags expressed by the APCs used for priming. TCR spectratyping of T suppressor cells showed oligoclonal usage of TCR-Vbeta families, indicating that xenostimulation of CD8+CD28- T cells results in Ag-driven selection of a limited Vbeta repertoire. Xenospecific T suppressor cells prevent the up-regulation of CD154 molecules on the membrane of Th cells, inhibiting their ability to react against the immunizing MHC class II xenoantigens. The mechanism of this suppression, therefore, appears to be blockade of CD154/CD40 interaction required for efficient costimulation of activated T cells.     

The use of a cationic liposome formulation (DOTAP) mixed with a recombinant tumor-associated antigen to induce immune responses and protective immunity in mice

The cationic liposome DOTAP is a well-known transfection reagent. It has been manufactured and approved for clinical use, is readily available, and can be easily used as an adjuvant. These characteristics prompted us to investigate the effectiveness of DOTAP as an adjuvant to induce immune responses and protective immunity in mice using baculovirus-derived carcinoembryonic antigen (bV-CEA) as a model antigen. Two routes of administration and a dose-response study of bV-CEA were used in BALB/c mice to define the magnitude of the immune response as well as the most effective route of immunization. The results demonstrate differences in antibody titers, immunoglobulin (Ig)G isotype, and T-cell responses between the intravenous (i.v.) or subcutaneous (s.c.) route of immunization. The titer of the anti-CEA antibodies induced by the s.c. immunization was greater than the response by i.v. immunization. The s.c. route enhanced the IgG2a/2b isotype, whereas i.v. immunization elicited primarily IgG1. T-cell proliferation responses and cytokine production paralleled the humoral response (i.e., production was higher in the s.c. immunized animals). No differences in immunological responses were seen using either 25 or 10 microg of bV-CEA three times. An amount of 25 microg of bV-CEA/DOTAP given by s.c. immunization was sufficient in protecting mice from the transplant of syngeneic tumor cells transduced with the human CEA gene. We conclude that the cationic liposome DOTAP may be a useful immunoadjuvant for active anti-tumor immunotherapy in future clinical trials. This study will help to define the most effective way to use such an adjuvant.     

Cellular mechanisms involved in protection against influenza virus infection in transgenic mice expressing a TCR receptor specific for class II hemagglutinin peptide in CD4+ and CD8+ T cells

Mice transgenic for a TCR that recognizes peptide110-120 of hemagglutinin of PR8 influenza virus in the context of MHC class II I-Ed molecules express the transgenes in both CD4+ and CD8+ T cells. We have found that these TCR-hemagglutinin (TCR-HA) transgenic mice display a significantly increased resistance to the primary infection with PR8 virus compared with the wild-type mice. The TCR-HA transgenic mice mounted significant MHC type II and enhanced MHC type I-restricted cytotoxicity as well as increased cytokine responses in both spleen and lungs after infection with PR8 virus. In contrast, the primary humoral response against PR8 virus was not significantly different from that of the wild-type mice. In vivo depletion and adoptive cell transfer experiments demonstrated that both CD4+ and CD8+ TCR-HA+ T cell subsets were required for the complete clearance of pulmonary virus following infection with a dose that is 100% lethal in wild-type mice. Whereas CD4+ TCR-HA+ T cells were necessary for effective activation and local recruitment of CD8+ T cells, CD8+ TCR-HA+ T cells showed a Th1-biased pattern and MHC type II-restricted cytotoxicity. However, in the absence of in vivo expression of MHC type I molecules on the infected cells, the protection conferred by the TCR-HA+ T cells was impaired, indicating that the enhanced MHC class I-restricted cytotoxicity due to TCR-HA+ CD4+ Th cells was a critical element for clearance of the pulmonary virus by the transgenic mice.     

Development of CD8 alpha/beta + TCR alpha beta intestinal intraepithelial lymphocytes in athymic nu/nu mice and participation in regional immune responses

On the basis of the CD8 coreceptor expression, T-cell receptor (TCR)alpha beta-bearing intestinal intraepithelial lymphocytes (i-IEL) segregate into two populations. The CD8 alpha alpha + TCR alpha beta i-IEL develop thymus independently, whereas the CD8 alpha beta + TCR alpha beta i-IEL are generally considered to be thymus dependent. Flow cytometry analysis revealed a distinct population of CD8 alpha beta + TCR alpha beta i-IEL in individual athymic nu/nu mice. The i-IEL encompassing CD8 alpha beta + TCR alpha beta cells expressed potent cytolytic and interferon-gamma-producing activities. These findings demonstrate that CD8 alpha beta + TCR alpha beta i-IEL can develop in nu/nu mice independently from a functional thymus and suggest that these cells, directly or indirectly, perform biological functions in the gut.     

Poliovirus vaccine vectors elicit antigen-specific cytotoxic T cells and protect mice against lethal challenge with malignant melanoma cells expressing a model antigen

Recombinant polioviruses expressing foreign antigens may provide a convenient vaccine vector system to induce protective immunity against diverse pathogens. Replication-competent chimeric viruses can be constructed by inserting foreign antigenic sequences within the poliovirus polyprotein. When inserted sequences are flanked by poliovirus protease recognition sites the recombinant polyprotein is processed to mature and functional viral proteins plus the exogenous antigen. It previously has been shown that poliovirus recombinants can induce antibody responses against the inserted sequences but it is not known whether poliovirus or vaccine vectors derived from it can elicit effective cytotoxic T lymphocyte (CTL) responses. To examine the ability of the recombinant poliovirus to induce CTL responses, a segment of the chicken ovalbumin gene, which includes the H2-Kb-restricted CTL epitope SIINFEKL, was cloned at the junction of the P1 and P2 regions. This recombinant virus replicated with near wild-type efficiency in culture and stably expressed high levels of the ovalbumin antigen. Murine and primate cells infected with the recombinant virus appropriately processed the SIINFEKL epitope and presented it within major histocompatibility complex class I molecules. Inoculation of mice with recombinant poliovirus that expresses ovalbumin elicits an effective specific CTL response. Furthermore, vaccination with these recombinant poliovirus induced protective immunity against challenge with lethal doses of a malignant melanoma cell line expressing ovalbumin.     

CD8+ T cells in intracellular bacterial infections of mice

In the normal course of an immune response, both CD4+ and CD8+ T cells respond to each of the bacterial pathogens we have discussed and both responses may be required for the most potent immunity to infection. In this discussion, we have focused on the ability of these organisms to prime CD8+ T-cell responses in vivo and the ability of CD8+ T cells as sole mediators of acquired immunity, to protect against infection. It is clear that the vacuolar location of bacterial pathogens such as Salmonella or Mycobacteria does not prevent in vivo priming of CD8+ T-cell responses to these pathogens. However, vacuolar localization may affect the potency of CD8+ T-cell responses under experimental conditions that assess the capacity of CD8+ T cells as the sole mediators of acquired immunity. In the case of cytoplasmic L. monocytogenes, clear evidence exists that antigen-specific CD8+ T cells, in the absence of immune CD4+ T cells, can provide substantial acquired immunity to naive mice. Similar clear experimental results with Salmonella and Mycobacteria are lacking. Such results would provide stronger support for vaccines that elicit CD8+ T-cell responses to these vacuolar pathogens. Although our discussion has focused on only three specific organisms, we suggest that detection of an in vivo CD8+ T-cell response to a bacterial antigen does not ensure that the response will be protective against infection in a vaccine setting. In the case of Salmonella and Mycobacteria, this issue remains unresolved.     

CD8+ T cells are activated during the early Th1 and Th2 immune responses in a murine Lyme disease model

T-helper responses following Borrelia burgdorferi infection in mice determine susceptibility to Lyme arthritis. The ratio of interleukin 4-positive, CD4+ to gamma interferon (IFN-gamma)-positive, CD4+ T cells was significantly greater in infected BALB/cJ mice than in infected C3H/HeJ mice. Increased numbers of IFN-gamma-producing cells predicted greater arthritis severity, and CD8+ T cells were the main source of IFN-gamma in both strains.     

Transgenic mice expressing human immunodeficiency virus type 1 in immune cells develop a severe AIDS-like disease

Panic disorder is a common and disabling condition which frequently leads to excessive reliance upon medical facilities. It is also closely associated with the development of agoraphobia. Medical approaches implicate disturbances of ascending brain noradrenergic and serotonergic systems, and support related pharmacotherapies. Contemporary psychological approaches focus upon misinterpretations of bodily sensations and an undue appreciation of the risk of life-threatening illness, and support cognitive/behavioral psychotherapies. A synthesis is possible by developing the view that the implicated ascending aminergic systems normally play a part in "effortful" or context-sensitive behavior. A relative failure of this under conditions of heightened arousal might be responsible for the rigid patterns of fear, belief, and behavior that characterize these patients. Clinical and research implications are discussed.     

An H2-T MHC class Ib molecule presents Listeria monocytogenes-derived antigen to immune CD8+ cytotoxic T cells

Mouse spleen T cells can adoptively transfer immunity to Listeria monocytogenes; this activity was markedly enhanced by stimulation with Con A in vitro before transfer. The enhanced and prolonged protection against L. monocytogenes in vivo was correlated with enhanced lysis in vitro of target cells infected with strains of L. monocytogenes that produce listeriolysin O (LLO). One of the targets of such cytotoxic cells from BALB/c (H2d) mice was a peptide that corresponded to amino acids 91 to 99 (p91-99) of the LLO molecule, which satisfies the binding motif of H2-Kd. Listeria-immune CD3+CD8+, but not CD3+CD8-, cells could also lyse H-2-incompatible, infected target cells. Immune cells from C57BL/6 (H2b) mice lysed allogeneic H-2d target cells infected with L. monocytogenes or a Bacillus subtilis transformant that secretes LLO, but did not lyse targets pulsed with p91-99. This H2-unrestricted cytolysis was therefore directed at a fragment of the LLO molecule other than p91-99. Listeria-infected bone marrow macrophages from congenic and recombinant strains of mice were lysed only when they shared the H2-T region or were Qa1-compatible with the immune cytotoxic cells; sharing of the H2-D, Q, or M region was insufficient. Thus, the immune response to L. monocytogenes included cytolytic CD8+ cells that recognized endogenously processed Listeria-derived Ags in the context of the class Ia H2-K molecule, as well as a class Ib H2-T molecule.     

CD4-mediated and CD8-mediated cytotoxic and proliferative immune responses to Toxoplasma gondii in seropositive humans

Both CD4+ and CD8+ cytotoxic T lymphocytes (CTL) are part of the human immune response to Toxoplasma gondii infection. To further our understanding of Toxoplasma immunity, we investigated factors influencing stimulation of CD4+ or CD8+ human T. gondii-specific immune cells. Both antigen-pulsed and Toxoplasma-infected antigen-presenting cells (APC) induced cell proliferation. Toxoplasma-infected APC elicited strong proliferation of CD4+ cells, but little or no proliferation of CD8+ cells, unless high antigen loads were used. Toxoplasma-infected APC stimulated specific cytotoxicity poorly or not at all, owing to death of stimulated cultures, whereas antigen-pulsed APC strongly elicited specific cytotoxicity. Cytotoxicity elicited by either type of APC resided exclusively in CD4+ T cells in polyclonal cultures. Thus, Toxoplasma-infected APC elicited stronger CD4-mediated than CD8-mediated cell proliferation and generated CD4+ CTL more readily than CD8+ CTL. Nonetheless, specific CD8+ memory cells were demonstrated, and rare CD8+ Toxoplasma-specific CTL were subcloned. Fixed Toxoplasma-infected APC (which induce CD8+ CTL) also elicited cell proliferation, but polyclonal cultures stimulated with these infected APC did not die. Unfixed Toxoplasma-infected APC strongly inhibited phytohemagglutinin-induced cell proliferation, whereas fixed APC did not. These data suggested that infected APC were inhibitory or lethal to some immune cells. Further investigations into interactions between immune cells and Toxoplasma-infected cells likely will help elucidate factors involved in the immunopathogenesis of Toxoplasma infection. As other intracellular parasites, including Plasmodium spp. and Leishmania spp., also elicit CD4+ CTL, such work may help establish paradigms governing immunity to intracellular parasites.     

Pulmonary lymphocyte recruitment: depletion of CD8+ T cells does not impair the pulmonary immune response to intratracheal antigen

CD8+ T cells predominate in the lungs in hypersensitivity and human immunodeficiency virus-related lymphocytic pneumonitis, but their role in the immunopathogenesis of lung disease is unknown. We have shown that in immunized mice depleted of CD4+ T cells, CD8+ T cells are recruited into the lungs in response to intratracheal antigen challenge with sheep red blood cells (SRBC) (J. Clin. Invest. 1991; 88:1244-1254) or to pulmonary infection with Pneumocystis carinii (Am. J. Respir. Cell Mol. Biol. 1991; 5:186-197), suggesting that recruitment of CD8+ T cells does not depend on CD4+ T cell-derived signals. Because CD8+ T cells themselves produce a variety of chemotactic and immunoregulatory cytokines, CD8+ T cells may be important participants in, and modulators of, pulmonary immune responses. To test this hypothesis, we examined the effects of CD8+ T cell depletion on the generation of a pulmonary immune response in vivo. We monitored the recruitment of mononuclear cells into lungs in the absence of CD8-dependent signals and measured the duration of pulmonary inflammation in the absence of suppressor CD8+ T cells. Primed mice were treated with anti-CD8 monoclonal antibody to deplete CD8+ T cells and subsequently were challenged intratracheally with 5 x 10(8) SRBC. At various times after challenge, total and differential cell counts and lymphocyte phenotypes were measured in bronchoalveolar lavage fluid by flow cytometry and lungs were scored histologically. We found that depletion of CD8+ T cells neither decreased recruitment of immune and inflammatory cells nor prolonged the pulmonary immune response.(ABSTRACT TRUNCATED AT 250 WORDS)     

CDw60: a marker for human CD8+ T helper cells

The existence of helper cells among the CD8+ T cell subset has been recognized for a long time. However, the phenotype of these cells has remained elusive. In this study, we provide evidence that the expression of the CDw60 antigen on human CD8+ T cell allows one to distinguish between CD8+ T helper cells and CD8+ T cells with cytotoxic and suppressor capacity. CDw60 monoclonal antibodies (mAb) recognize the 9-O-acetylated disialosyl group on ganglioside GD3 expressed on 20-40% of CD8+ cells. By use of the direct and indirect mAb-rosetting technique, we were able to isolate the CDw60+CD8+ and CDw60-CD8+ cells at high purity. The alloantigen-specific cytotoxic activity of CD8+ cells resided entirely in the CDw60- population. Helper and suppressor capacity of both CD8 subsets was assayed by the pokeweed mitogen-induced differentiation of B cells into immunoglobulin-secreting cells. These studies clearly indicate that the CDw60+CD8+ subset provided substantial help to B lymphocytes, whereas the CD8+ cells with the CDw60- phenotype were suppressing B cell differentiation. Both subsets produced similar amounts of interleukin 2 (IL-2) after stimulation with phytohemagglutinin. Activation with phorbol myristate acetate in combination with Ca-ionophore induced IL-4 secretion in both populations, but preferentially in the CDw60+ subset, whereas the vast majority of interferon gamma was produced by the CDw60-CD8+ cells. When used in combination with other markers, CDw60 may prove to be useful in defining CD8+ subsets with reciprocal functional activities.     

Characterization of circulating CD4+ CD8+ lymphocytes in healthy individuals prompted by identification of a blood donor with a markedly elevated level of CD4+ CD8+ lymphocytes

During flow cytometric analysis of lymphocytes from healthy donors, we identified a donor (donor A) with 22% CD4+ CD8+ cells (versus values of < 4% for 65 other controls). To determine if CD4+ CD8+ cells from donor A and other controls were similar, we first defined the phenotypic profile of control CD4+ CD8+ cells. Enriched CD4+ CD8+ cell populations for 10 controls were prepared by a two-step positive selection scheme with anti-CD4-coated magnetic beads and anti-CD8-coated culture flasks; the selected population averaged 69% CD4+ CD8+ cells and 31% CD4+ CD8- cells. For all 10 controls, two subsets of CD4+ CD8+ cells, CD4dim CD8bright and CD4bright CD8dim, were observed. Phenotypic profiles of these two CD4+ CD8+ subsets were defined by pairing anti-CD8 with other monoclonal antibodies, and the profiles were compared with each other and with those of CD4+ CD8-, CD4- CD8bright, and CD4- CD8dim cells. CD8bright and CD4bright CD8dim cells differed in their proportions of CD62-L+ cells and in their levels of CD11a and CD2 expression. Both CD4+ CD8+ subsets resembled CD4+ CD8- cells in CD45RA, CD45RO, and CD25 expression; the comparable CD- CD8+ cells in CD62-L expression; and CD4- CD8bright cells in CD11b, CD11b, CD16/56, and CD28 expression. CD38 expression in both CD4+ CD8+ subsets was decreased compared with those of other cell subsets. Whereas control CD4+ CD8+ cells averaged 33% CD4dim CD8bright, CD4+ CD8+ cells from donor A were > 90% CD4dim CD8bright. Donor A CD4dim CD8bright cells exhibited proportional decreases in CD25 and CD62-L expression and increases in CD11b and CD54 expression compared with those of control CD4dim CD8bright cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characteristics and maintenance of CD8+ T-cell clones found in old mice

Old mice, like old human beings, contain large clones of CD8+ T-cells. These cells grow poorly in tissue culture, therefore it is difficult to maintain the cells in vitro. The cells can be grown after transfer to sublethally irradiated mice. This technique will be useful in further studies on the properties of the cells. Based on observations from such transfer experiments, we conclude that: (1) expansion of the T-cell clones in recipients is dramatic but slow; (2) chance events caused by endogenous antigens or gene mutations rather than exogenous antigens may account for the expansion of these clones; and (3) the expanded T-cell clones are benign and do not cause malignancies.