The antigen-bearing eye and the spleen are indispensable in maintaining anterior chamber-associated immune deviation

PURPOSE: To investigate the role of the eye and the spleen in maintaining suppression of delayed-type hypersensitivity (DTH) after anterior chamber (AC) inoculation of allogeneic splenocytes. METHODS: Suppression of DTH response was tested in BALB/c mice after AC inoculation of allogeneic B10.D2 splenocytes. Seven days after AC injection, the antigen-inoculated eyes were enucleated or the spleens were removed. After enculeation or splenectomy at different time intervals, DTH responses in groups of the BALB/c mice were examined. Spleen components obtained from BALB/c mice that had been primed by B10.D2 splenocytes in the AC 7 days earlier were transferred intravenously to groups of naive syngeneic acceptors. At various intervals after adoptive transfer, variations of DTH responses were tested. RESULTS: Inoculation of B10.D2 splenocytes to the AC of BALB/c mice induced antigen-specific suppression of DTH. Either enucleation of the antigen-inoculated eyes or splenectomy weakened the DTH-suppressive effect within 5 weeks and abolished it within 9 weeks, whereas the mice retaining both antigen-inoculated eyes and spleens maintained longstanding DTH suppression. Adoptive transfer of spleen components to syngeneic acceptors demonstrated DTH suppression for only 3 weeks. CONCLUSIONS: The antigen-inoculated eye and spleen are required for long-standing suppression of DTH after AC inoculation of allogeneic splenocytes.     

Allogeneic cell therapy for a murine mammary carcinoma

The effect of allogeneic cell therapy on tumor growth was studied in a murine model of mammary carcinoma (4T1) as an experimental model of solid tumors in humans. i.v. inoculation of 4T1 (H-2d) cells into syngeneic mice [BALB/c or (BALB/cXC57BL/6)F1] (F1) carrying the H-2d histocompatible antigens results in tumor colonies in the lungs that finally cause the death of all of the mice. Sublethally irradiated F1 mice were inoculated with 4T1 cells to simulate minimal residual disease and with immunocompetent splenocytes derived from naive donors of F1 (syngeneic), BALB/c (syngeneic to the tumor but semiallogeneic to the host), or C57BL/6 (allogeneic to the tumor and semiallogeneic to the host) mice. The survival of F1 tumor-bearing mice that were treated with allogeneic C57BL/6 splenocytes was significantly prolonged (P < 0.02) compared with hosts given F1 or BALB/c-derived splenocytes that are syngeneic to 4T1 tumor cells. Adoptive transfer of lung cells that were isolated from F1 primary mice inoculated with 4T1 cells and syngeneic BALB/c or F1 splenocytes led to local tumor growth and death in secondary recipients. In contrast, only 1 of 22 secondary recipients developed tumors when inoculated with lung cells derived from F1 mice given allogeneic C57BL/6 splenocytes. All of the 21 secondary hosts survived disease-free for a follow-up time of >200 days. These results indicate that immunocompetent cells allogeneic to the mammary carcinoma cells were able to inhibit tumor development in the primary hosts and to prevent tumor growth in the adoptive recipients, which suggests that allogeneic cell therapy may be an efficient antitumor tool to eradicate minimal residual disease in human solid tumors.     

Anterior chamber inoculation of splenocytes without Fas/Fas-ligand interaction primes for a delayed-type hypersensitivity response rather than inducing anterior chamber-associated immune deviation

The inoculation of antigens into the anterior chamber (AC) of the eye induces an antigen-specific immune response that inhibits delayed-type hypersensitivity (DTH). This regulatory response is known as anterior chamber-associated immune deviation (ACAID). The ACAID response appears to be complex, as it can be elicited by a wide variety of soluble and cell-associated antigens, including foreign, self, tumor, and alloantigens. To evaluate the contribution of Fas/Fas ligand (FasL) interaction to the induction of ACAID to alloantigens, gld and lpr mutant mice were used in conjunction with normal C3H, MRL, and BALB/c mice. ACAID was induced by inoculation of non-irradiated splenocytes from donor mice into the AC of various recipients. After 1 week, recipients were primed intradermally with donor splenocytes. One week later DTH was measured by ear swelling. C3Hgld mutants lacking functional FasL did not develop ACAID after the AC inoculation of BALB/c splenocytes. Conversely, the AC inoculation sensitized these mutants. MRL/pr mutants, which lack Fas, developed ACAID following inoculation of BALB/c cells. AC inoculation of lpr splenocytes did not induce ACAID, but sensitized C3H recipients. Treatment of the AC inoculum with an anti-Fas antibody blocked ACAID induction in a transient manner, as the recipients developed ACAID later. These results show that interaction of the Fas and FasL is required to induce ACAID to allogeneic cells. In the absence of Fas expression on donor splenocytes, or FasL expression by the recipient, AC inoculation primes for a DTH response rather than inducing ACAID.     

Experimental murine Trypanosoma congolense infections. I. Administration of anti-IFN-gamma antibodies alters trypanosome-susceptible mice to a resistant-like phenotype

The mechanisms regulating resistance or susceptibility to African trypanosomes have been enigmatic. In this study, we assessed the production of several cytokines (IL-4, IFN-gamma, and TNF-alpha) in vivo and in vitro using genetically susceptible (BALB/c) or resistant (C57BL/6) mice infected with cloned Trypanosoma congolense and the role of these cytokines in pathogenesis of this infection. Plasma of infected BALB/c mice contained higher levels of IL-4 and IFN-gamma than the plasma of infected C57BL/6 mice. Conversely, plasma TNF-alpha levels were elevated significantly in the resistant mice relative to the susceptible ones. Splenic IFN-gamma mRNA appeared earlier and were maintained at higher levels in infected BALB/c than in C57BL/6 mice. Both spontaneous and Con A-induced secretions of IL-4 and IFN-gamma by splenocytes from infected BALB/c mice were significantly higher than those from their C57BL/6 counterparts. Con A-induced proliferation of splenocytes from infected BALB/c mice was progressively suppressed. Nitric oxide was not involved in this suppression, but the suppression was positively correlated with IFN-gamma secretion. Addition of neutralizing Abs to IFN-gamma to cultures of Con A-stimulated spleen cells from infected BALB/c mice effectively reversed this suppression. Furthermore, administration of anti-IFN-gamma Abs to BALB/c mice early during infection dramatically shifted the phenotype of these susceptible mice to a more resistant-like phenotype, as expressed by a low and undulating parasitemia and a >300% increase in survival period. These results strongly suggest that the enhanced induction and secretion of IFN-gamma during T. congolense infections contribute to the relative susceptibility of BALB/c mice to the disease.     

Effect of emotional stress on the frequency of chromosome aberrations in the bone marrow cells of mice

The chromosome aberration rate was studied in bone marrow cells of C57BL/6, CBA and BALB/c mice before and after emotional stress. After "the opened field" experiment the chromosome aberration rate in C57BL/6 and CBA mice increased while that in BALB/c mice remained unchanaed. The mutagenic effect was prevented by phenazepam.     

Immune response to the copolymer of L-glutamic acid50-L-tyrosine50 (GT): effect of adult thymectomy and genetic control of immune suppression

The secondary antibody response to GT and GT-MBSA (GT coupled to methylated bovine serum albumin) and the ability to generate specific suppressor cells after GT preimmunization were examined in the auto-immune NZB strain and in normal and adult thymectomized C3H, BALB/c and CBA mice. As previously shown C3H, BALB/c and CBA mouse strains do not mount a secondary anti-GT antibody response after immunization with GT. On the contrary NZB mice where shown to develop a small but significant anti-GT antibody production. All the mice tested produced anti-GT antibodies after immunization with GT-MBSA. Adult thymectomy greatly decreased this anti-GT antibody response in BALB/c, C3H and CBA mice, suggesting the involvement of a short-lived T-cell subpopulation in the development of an optimal anti-GT-MBSA response. Preimmunization with GT suppressed the secondary antibody response to GT-MBSA in CBA and BALB/c mice but not in NZB and C3H mice, although all these strains bear the H-2-linked Is genes. This indicates an additional genetic control on the generation of GT-specific suppressor cells.     

Glucose-modified low density lipoprotein enhances human monocyte chemotaxis

In response to stimulation with immobilized anti-CD3 antibody, splenocytes from C57BL/6 and BALB/c mice principally produced INF-gamma and IL-4, respectively. However, both splenocytes equally proliferated in response to ConA. We compared the changes after inoculation with BCG (1 mg/mouse) in their capacity to produce IL-4 or IFN-gamma in response to anti-CD3 antibody and to proliferate in response to ConA. Splenocytes from C57BL/6 and BALB/c mice, that had been inoculated with BCG 4 weeks before, produced IFN-gamma with diminished IL-4 production in response to anti-CD3 antibody. Furthermore these splenocytes became anergic to ConA stimulation and died due to cell apoptosis in stead of proliferation. However, we observed the strain difference at 12 weeks after BCG-infection. BCG-primed C57BL/6 splenocytes, that continuously produced IFN-gamma in response to anti-CD3 antibody, failed to proliferate in response to ConA. In contrast, BCG-primed BALB/c splenocytes, that increased IL-4 production but decreased IFN-gamma production when stimulated with anti-CD3 antibody, could proliferate well in response to ConA. Since the splenocytes of BALB/c mice became ConA responsive along with their shifting from Th1 dominant immune response at 4 weeks to Th2 dominant immune response at 12 weeks after BCG-inoculation, IL-4 was assumed to play a crucial role in activation of anergic T cells. Therefore, we stimulated splenocytes from both strains of mice infected with BCG 4 weeks before with ConA in the presence or absence of IL-4. Splenocytes from BCG-infected BALB/c mice showed marked proliferation, while those from BCG-infected C57BL/6 mice failed. We found that IL-4 protected against ConA-induced cell apoptosis in BALB/c splenocytes but not C57BL/6 splenocytes.     

Antibody response to pneumococcal polysaccharide vaccine in young, adult and old mice

The anti-pneumococcal antibody response was studied in young (5-week-old) and adult (10-week-old) BALB/c and CBA/J mice and in adult (9-10-week-old) and old (12-, 18- and 24-month-old) AB6F1 and B6D2F1 mice after s.c. immunization with a 23-valent pneumococcal polysaccharide vaccine. Both young and adult mice showed a significant IgM antibody response to the vaccine 6 days after immunization with 1-11 micrograms antigen. There were significant immune responses to serotypes 1, 2, 4 and 7F in contrast to small responses to serotypes 14, 19F and 23F after immunization with the vaccine. One month after immunization, there were only marginal differences in IgM anti-pneumococcal antibody levels to the vaccine (anti-PPS) between immunized and unimmunized BALB/c mice, whereas in CBA/J mice the anti-PPS remained higher in immunized than in unimmunized mice. Immunization of old mice induced a significant IgM antibody response 6 days after immunization, but the anti-PPS thereafter decreased rapidly towards preimmunization values in AB6F1 mice. A significant IgG anti-PPS was not detected in any of the mice studied. The IgA anti-PPS tended to vary over time with no consistent pattern. It is important to carefully consider age and strain of the mice used when studying the immune response to pneumococcal polysaccharide antigens.     

The in vitro expression patterns of individual type I interferon genes in Newcastle disease virus infected murine splenocytes and fibroblasts

Murine type I interferon levels present in mice sera following Newcastle disease virus infections are influenced by the If-1 locus. Sera interferon levels in C57BL/6 mice (If-1h allele) are 10- to 15-fold higher than in BALB/c mice (If-1(1) allele). The B6.C-H-28c strain, which carries BALB/c If-1(1) allele on C57BL/6 genomic background, has low interferon levels in sera. This study examined the expression of interferon alpha 1, alpha 4, alpha 5, alpha 6, alpha 9 and beta mRNAs at 7 hr after Newcastle disease virus infection of primary cells (splenocytes and mouse embryo fibroblasts) from C57BL/6, B6.C-H-28c and BALB/c mouse genotypes. Total RNA from these cells was reverse transcribed and all known type I interferon subtypes were amplified. The products were identified by differential hybridization to a panel of subtype specific oligonucleotides. The results show that the pattern of interferon subtypes examined in splenocytes did not differ between If-1h and If-1(1) allele carrying C57BL mice. However, when the genotype was different (BALB/c splenocytes) the pattern of type I interferon mRNAs seen was altered. This genotype-dependent expression was also seen in newcastle disease virus infected fibroblasts. Within a given mouse strain, there were also differences in the subtype response patterns detected in fibroblasts compared with those seen in splenocytes. In conclusion, the present study indicates that mouse genotype appears to be a major determinant of the subtype response pattern seen and tissue specific pattern differences are present within a given mouse genotype.     

An in vitro model for infection with Leishmania major that mimics the immune response in mice

By using a primary in vitro response specific for Leishmania major, normal T cells from resistant CBA/CaH-T6J and susceptible BALB/c mice commit to a Th1 and a Th2 response, respectively. Since commitment occurred, we measured the production of gamma interferon (IFN-gamma), interleukin-1 (IL-1), IL-2, IL-4, IL-5, IL-10, and IL-12, prostaglandin E2 (PGE2), transforming growth factor beta (TGF-beta), and nitric oxide in the first 7 days of the response to identify factors that are critical for Th1 and Th2 development. While cells from resistant CBA mice produced more IFN-gamma, IL-10, and nitric oxide, cells from susceptible BALB/c mice produced more IL-1alpha, IL-5, PGE2, and TGF-beta. Although substantial amounts of IL-12 were detected, IL-12 did not associate with either Th1 or Th2 development. We did not anticipate that cells from resistant CBA mice would make more IL-10 in vitro. However, this also occurred in vivo since CBA mice produced substantial amounts of IL-10 following infection with L. major. Moreover, adding anti-IL-10 to primary in vitro responses enhanced production of IFN-gamma and nitric oxide by cells from CBA and BALB/c mice. Therefore, IL-10 cannot be regarded as a cytokine that associates with susceptibility to infection with L. major. Finally, the data presented here suggest that a collection of factors that can be produced by accessory cells influence Th commitment (e.g., IL-1, PGE2, and TGF-beta favor Th2 development).     

A monoclonal antibody against a human B lymphoblastoid cell line induces tumor regression in mice

We have developed a monoclonal antibody (BAT) to Daudi B lymphoblastoid cell line membranes. The antibody was selected for its ability to stimulate lymphocyte proliferation. Splenocytes of BALB/c or C57BL mice given i.v. injections of 10 micrograms/mouse of BAT exhibited increased proliferation and cytotoxic activity. A single i.v. administration of BAT monoclonal antibody 2 weeks after B16 melanoma cell inoculation resulted in a striking antitumor effect as manifested by the elimination of lung metastases and prolonged survival of the treated mice. BAT monoclonal antibody was also effective in the regression of tumors in mice bearing 3LL (Lewis lung carcinoma) and MCA-105 (fibrosarcoma). Transfer of 10(7)-10(8) splenocytes from mice that had been given injections of BAT to B16- or 3LL-inoculated recipients led to a reduction of lung metastases. Splenocytes from B16-inoculated mice that were cured by BAT were more effective than those from mice treated with BAT alone against recipients bearing either B16 or 3LL tumors. The antitumor activity of BAT is related to its immunostimulatory properties.     

Uncovering subdominant cytotoxic T-lymphocyte responses in lymphocytic choriomeningitis virus-infected BALB/c mice

The cytotoxic T-lymphocyte response against lymphocytic choriomeningitis virus (LCMV) in BALB/c mice is predominantly directed against a single, Ld-restricted epitope in the viral nucleoprotein (residues 118 to 126). To investigate whether any Kd/Dd-restricted responses were activated but did not expand during the primary response, we used a BALB/c mutant, BALB/c-H-2dm2, which does not express the Ld molecule. Splenocytes from LCMV-infected BALB/c mice were transferred into irradiated BALB/c-H-2dm2 mice and rechallenged with LCMV. Thus, they were exposed to an antigenic stimulus without the involvement of the immunodominant Ld-restricted epitope. In this adoptive transfer model, the donor splenocytes protected the recipient mice against chronic LCMV infection by mounting a potent Kd- and/or Dd-restricted secondary antiviral response. Analysis of a panel of Kd binding LCMV peptides revealed that residues 283 to 291 from the viral glycoprotein (GP(283-291)) comprise a major new epitope in the adoptive transfer model. Because the donor splenocytes were first activated during the primary infection in BALB/c mice, the GP(283-291) epitope is a subdominant epitope in BALB/c mice that becomes dominant after rechallenge in BALB/c-H-2dm2 mice. This study makes two points. First, it shows that subdominant CTL responses can be protective, and second, it provides a general experimental approach for uncovering subdominant CTL responses in vivo. This strategy can be used to identify subdominant T-cell responses in other systems.     

Strain differences in susceptibility of female mice to 1,2-dimethylhydrazine

C3H, CBA, C57BL/6j, (CBA x C57BL/6j)F1, BALB/c, DBA/2, C3HA and AKR female mice were treated with 25 weekly s.c. injections of a solution of 1,2-dimethylhydrazine (DMH) in water at a dose level of 8 mg/kg body weight. BALB/c mice appeared to be most sensitive to the induction of epithelial colorectal (93.3%) and anal tumours by DMH. There was, however, a dissociation between the severity of the macroscopical tumour lesions in the colon of BALB/c mice and their relatively weak tendency to infiltrative growth. C3HA mice were more resistant to the induction of intestinal tumours (30.9%) but the tumours showed a deep invasion into the intestinal wall. There was no correlation between the strains and within a given strain between the development of colorectal and anal neoplasms. C3H and CBA mice strains developed a high incidence of uterine sarcomas (37.5 and 40.7%, respectively) which were not found at all in BALB/c, DBA/2 and C3HA mice and which appeared in C57BL/6j and AKR mice at low frequency (2.7 and 7.7%, respectively). C57BL/6j, BALB/c, DBA/2 and C3HA mice developed haemorrhagic lesions of the ovaries (35.1, 46.7, 62.9 and 85.7%, respectively). These lesions, which led to peritoneal haemorrhage, were one of the main causes of death in C3HA and DBA/2 strains. It seems that, with the exception of AKR mice, an inverse relationship exists between the occurrence of haemorrhagic ovarian lesions and development of uterine sarcomas in female mice treated with DMH.     

The characteristics of the development of the immune function in the transplanted spleen of newborn mouse pups in recipients of different ages. 2. The effect of the thymus on the functional development of the transplant]

The effect of the neonatal thymus grafting or "Thymostimulin" administration on the cellularity, cell composition, immune, response to SRBC and proliferative activity of T- and B-cells in vitro were determined in neonatal spleen grafted CBA/Ca female mice of different ages. Analysis of the thymus graft effect on the T- and B-cells content in the spleen transplant from the adult and old recipients demonstrated no differences. The neonatal thymus grafting led to the essential increase of the immune response, spleen cellularity and to the diametrically opposed changing from negative to positive of the sign of the correlation coefficient between the T-cells content and the cellularity of the neonatal spleen in the old recipients. The similar effect of the neonatal thymus grafting was revealed in respect of correlative connection between content of the T-cells and PFCs in spleen grafted to the old recipients too. The "Thymostimulin" injection led only to the increase of the spleen transplant cellularity. These results suggests that the young thymic microenvironment is essential for the normal T-cells differentiation and for its normal function in the neonatal spleen transplant.     

Marked prolongation of rat skin xenografts induced by intrathymic injection of xenogeneic splenocytes and a short course of rapamycin in antilymphocyte serum-treated mice

The effect of intrathymic (IT) injection of donor splenocytes and a short course of rapamycin (Rapa) treatment on rat to mouse skin xenograft survival was investigated. ACI rat skin xenografts were transplanted to (C57BL/6 x A)F1 mice treated with rabbit anti-mouse lymphocyte serum (ALS) on days -1, +2, and +4 relative to skin grafting on day 0. Fifty million donor-type splenocytes were injected intrathymically on day 7 after transplantation. Rapa was given intraperitoneally every other day from day 0 to day 12 at a dose of 3.0 mg/kg. Prolonged skin xenograft survival was observed in ALS- and Rapa-treated recipients (no IT injection) with a median survival time of 47 days. However, skin graft survival was markedly more prolonged in the group treated with ALS, Rapa, and IT injection of donor splenocytes did not have a beneficial effect on skin xenograft survival in ALS-treated recipients. An increased presence of donor-type cells was observed in the thymus of the ALS- and Rapa-treated recipients for 7 days after IT injection of donor splenocytes. In conclusion, a short course of Rapa markedly augments rat skin xenograft survival in ALS-treated mice injected intrathymically with donor-type splenocytes.     

Immunostimulation with muramyl dipeptide and its desmethyl analogue: Studies of non-specific resistance to pulmonary blastomycosis in inbred mouse strains

N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) protected against pulmonary blastomycosis when given prophylactically to BALB/c mice. Its desmethyl analogue (DM-MDP) had a similar effect. In C3H/HeJ, the effect was less marked. Early treatment after infection, with MDP and DM-MDP, had a modest effect in C3H/HeJ and BALB/c respectively, whereas late treatment had no effect in any mouse strain. No effect could be demonstrated with challenge sizes producing too lethal a model or minimal lethality, or in DBA/2J or young BALB/c mice. The effects in various strains do not correlate with differing effects on nonspecific immunostimulation in these strains. Immunostimulation with glycopeptides deserves further study in prophylaxis or therapy of fungal infection.     

Time course of the changes in prednisolone pharmacokinetics after co-administration or discontinuation of rifampin

After intraperitoneal immunization by different sheep erythrocytes doses (1 x 10(6) - 1 x 10(8)) in the spleen of CBA strain and (CBA x C57Bl/6)F1 hybrid mice short-living suppressor cells, which are able to inhibit mature IgM-but not IgG-plaque-forming cells have been revealed. The suppression degree is in direct dependency on the delayed type hypersensitivity effectors activity. The revealed suppressor splenocytes are Thy-1-positive, do not adhere to plastic, are antigen-specific, require the H-2 complex restriction, are unable to homing into regional lymph nodes, their induction is abolished by administration of 200 mg/kg, but not 20 mg/kg of cyclophosphamide. It has been shown that T-suppressors of delayed type hypersensitivity are able to carry out the function of contrasuppressors.     

Regression of established mouse leukemia by GM-CSF-transduced tumor vaccine: implications for cytotoxic T lymphocyte responses and tumor burdens

This study investigated the therapeutic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on a mouse leukemia model. By using a retroviral vector, mouse GM-CSF cDNA was transduced into a highly tumorigenic T leukemia cell line, RL male 1. Injection of GM-CSF-secreting RL male 1 cells into syngeneic BALB/c mice elicited protective immunity in the animals, which could regress preestablished tumors introduced either by a subcutaneous or in an intravenous route. However, the therapeutic effects were less prominent in the mice inoculated with a large tumor load or in mice treated later. Winn tests further demonstrated that the splenocytes from the late-treated group conferred poorer protective effects in terms of reducing the growth of parental RL male 1 cells in naive mice than the splenocytes from the early-treated group. Nonetheless, upon stimulation in vitro, the activity of tumor-specific cytotoxic T lymphocytes (CTL) was comparable in the splenocytes of both groups of mice. Histological analysis also indicated that the CD8+ T cells appeared as early as 3 days following vaccination at the vaccine sites and at the tumor sites in both groups of mice. Above observations implied that the T cells in the animals bearing large tumors appeared to be in a state of suppression or anergy. Systematic histological analyses for 2 weeks provided further insight into various infiltrates at the vaccine sites and at the tumor sites in response to the inoculation of GM-CSF-secreting tumor vaccine.     

Immunoregulation in experimental murine Trypanosoma congolense infection: anti-IL-10 antibodies reverse trypanosome-mediated suppression of lymphocyte proliferation in vitro and moderately prolong the lifespan of genetically susceptible BALB/c mice

We infected highly susceptible BALB/c and relatively resistant C57BL/6 mice with cloned Trypanosoma congolense and followed the effects of these infections on the circulating parasite numbers, mouse mortality and cytokine expression. C57BL/6 mice controlled their parasitaemia and survived for up to 163 +/- 12 days, while BALB/c mice could not control their parasitaemia and succumbed to the infection within 8.4 +/- 0.5 days. Susceptible BALB/c mice had dramatically higher plasma levels of IL-10 than the resistant C57BL/6 mice from day 7 forward. This was preceded by an earlier and higher level induction of splenic IL-10 messenger RNA (mRNA) expression in the infected BALB/c mice. There was a strong negative correlation between the splenocyte proliferative responses to Concanavalin-A (Con-A) and their production of IL-10 in these infected BALB/c mice. Co-treatment of the Con-A-stimulated spleen cell cultures with monoclonal anti-IL-10 antibodies, but not isotype-matched control antibodies, could completely reverse this suppression of the splenocyte proliferative response. Finally, in three experiments, anti-IL-10 antibody treatment in vivo reduced the peak circulating parasitaemia of infected BALB/c mice by 43% and increased their median survival periods by 38% relative to isotype-matched control antibody-treated mice.