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.     

Molecular characterization and functional analysis of murine interleukin 4 receptor allotypes

The murine interleukin 4 receptor (IL-4R) exists as a transmembrane protein transducing pleiotropic IL-4 functions, or as soluble (s)IL-4-binding molecule with potent immunoregulatory effects. In this study we identified and characterized a murine IL-4R allotype. Sequence analysis of the IL-4R cDNA of BALB/c mice revealed 18 base substitutions leading to three extracellular and five cytoplasmic amino acid changes when compared with the published IL-4R sequence of C57BL/6 mice. Analyses with allotype-specific mAbs revealed that AKR/J and SJL/J mice possess the newly identified BALB/c IL-4R allotype whereas the IL-4Rs of C3H, CBA, DBA-2, and FVB/N mice are identical to that of the C57BL/6 mouse. The extracellular Thr49 to Ile substitution abrogates one N-glycosylation site in the naturally occurring BALB/c IL-4R as well as in the experimentally point mutated C57BL/6-T49I sIL-4R, and both molecules display a nearly threefold reduction in IL-4-neutralizing activity compared to the C57BL/6 sIL-4R. In line with this, a significantly enhanced dissociation rate of IL-4 was detected for the BALB/c IL-4R allotype by surface plasmon resonance and in radioligand binding studies with IL-4R-transfected cell lines. These findings suggest that the altered ligand binding behavior of the newly described IL-4R allotype may influence the IL-4 responsiveness, thus contributing to the diverse phenotypes of inbred mouse strains in IL-4-dependent diseases.     

Genetic studies of daily variations of first-step enzymes of monoamines metabolism in the brain of inbred strains of mice and hybrids. II. Daily variations of tyrosine hydroxylase activity in the locus coeruleus

Daily variations of tyrosine hydroxylase (TH) activity in the locus coeruleus of 3 inbred strains of mice (BALB/c; C57BL6; C57Br) and the F1 hybrids obtained from BALB/c and C57BL/6 are discussed. Precise characteristics of the circadian rhythms were observed in each strain. They were found significantly different in two genetically pure parents (BALB/c and C57BL6). In their two F1 hybrids the daily variation of TH activity was similar to that observed in one of the parents (C57BL6). This strongly suggests selective and genetically controlled mechanisms of regulation responsible for the daily variation of TH activity in the locus coeruleus of mice.     

Cross-reactivity of the NPa and NPb idiotypic responses of BALB/c and C57BL/6 mice to (4-hydroxy-3-nitrophenyl)acetyl (NP)

A comparative antigenic analysis was carried out to determine whether cross-reactivity exists between the major idiotypic responses to (4-hydroxy-3-nitrophenyl)acetyl (NP) in BALB/c and C57BL/6 mice. Extensive cross-reactivity exists between the NPa (BALB/c) and NPb (C57BL/6) allotype-linked idiotypic responses to NP. The cross-reactive determinants of the NPb idiotype are confined to one particular group of NPb-positive monoclonal antibodies. The extent of cross-reactivity between this group of C57BL/6 antibodies and idiotype-positive monoclonal antibodies of BALB/c is so great that they cannot be readily distinguished as NPb- or NPa-positive antibodies with polyclonal anti-idiotypic reagents. That this cross-reactivity is not unique to monoclonal antibodies was confirmed by the demonstration of these cross-reactive determinants in the immunesera of individual BALB/c and C57BL/6 mice. Additionally, evidence was obtained from these experiments and from earlier ones from this laboratory which suggests that the BALB/c idiotypic response to NP-protein conjugate is more homogeneous than the C57BL/6 idiotypic responses.     

Genetic influences on latent inhibition.

The present study examined the development of latent inhibition in a number of inbred strains of mice. C57BL/6J, DBA/2J, C3H/Ibg, BALB/cByJ, A/J, CBA/J, 129/SvevTac, 129/SvJ, and AKR/J mice were screened for the development of latent inhibition. The latent inhibition paradigm involved 1 day of either 40 preexposures to the conditioned stimulus (CS) or no preexposure. On the following training day, the CS was twice paired with a shock unconditioned stimulus (US). On a subsequent test day, the strength of the CS—US association was measured. Mice preexposed to the CS should show a weaker CS—US association, which would reflect development of latent inhibition. Significant between-strain differences existed. The 129/Svev, C57BL/6, BALB/cByJ, AKR, and DBA/2 mice developed latent inhibition, but 129/SvJ, CBA, A, and C3H mice did not. Thus, genetic variance contributes to variability in the development of latent inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strain difference in the induction of T-cell activation-associated, interferon gamma-dependent hepatic injury in mice

A single intravenous injection of concanavalin A (Con A) induces T-cell activation-associated inflammatory injury selectively in the liver. This study investigated the strain difference in the development of Con A-induced hepatic injury. Normal C57BL/6 and BALB/c spleen cells produced comparable levels of T-cell-derived lymphokines (interferon gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], and interleukin-2 [IL-2]) following in vitro stimulation with Con A. A single intravenous injection of Con A to C57BL/6 mice induced the plasma levels of TNF-alpha and IL-2 comparable with or slightly higher than those observed in BALB/c mice, whereas the same treatment resulted in an apparently lower level of IFN-gamma production in C57BL/6 mice. RNA from livers of Con A-treated C57BL/6 mice exhibited lower levels of IFN-gamma mRNA than RNA of BALB/c livers. Unexpectedly, a dramatic difference in the severity of hepatic injury was observed between C57BL/6 and BALB/c. Namely, the peak alanine transaminase (ALT) level was more than 15,000 U/L and inducible as early as 8 hours after injection of 0.2 mg Con A per mouse in the C57BL/6 strain, whereas the peak was approximately 3,000 U/L and induced as late as 24 hours after Con A injection in the BALB/c strain. The increase in plasma ALT levels was limited to less than 10% by injection of anti-IFN-gamma monoclonal antibody (mAb) in both strains. The C57BL/6 strain inducing lower levels of IFN-gamma exhibited higher IFN-gamma responsiveness as exemplified by the intrahepatic expression of an IFN-gamma-inducible gene, an inducible type of nitric oxide (NO) synthase (iNOS). These results indicate that, while IFN-gamma produced in vivo by activated T cells induces hepatic injury, there exists a striking strain difference in the induction of IFN-gamma-dependent hepatic injury.     

Genetic influence on neurogenesis in the dentate gyrus of adult mice

To address genetic influences on hippocampal neurogenesis in adult mice, we compared C57BL/6, BALB/c, CD1(ICR), and 129Sv/J mice to examine proliferation, survival, and differentiation of newborn cells in the dentate gyrus. Proliferation was highest in C57BL/6; the survival rate of newborn cells was highest in CD1. In all strains approximately 60% of surviving newborn cells had a neuronal phenotype, but 129/SvJ produced more astrocytes. Over 6 days C57BL/6 produced 0.36% of their total granule cell number of 239,000 as new neurons, BALB/c 0.30% of 242,000, CD1 (ICR) 0.32% of 351,000, and 129/SvJ 0.16% of 280,000. These results show that different aspects of adult hippocampal neurogenesis are differentially influenced by the genetic background.     

Gastrojejunostomy in proximal resection of the stomach

Correlations between specific binding of labeled adrenoligands in the frontal cortex and hypothalamus and peripheral blood plasma testosterone were studied in BALB/cLac, CBA/Lac, and S57BL/6J male mice. A negative correlation was detected between blood testosterone and the extent of specific binding of 3H-clonidine, a 1.6 nM alpha 2-adrenoceptor agonist, in the hypothalamus. No correlations were revealed between specific binding of 3H-clonidine in the frontal cortex and binding of the rest radioligands (0.4 nM alpha 1-adrenoceptor antagonist 3H-prazosin and 1.6 nM beta-adrenoceptor antagonist 3H-dihydroalprenolol) in both brain segments and blood testosterone level. Further experiments in six mouse strains (A/He, BALB/cLac, CBA/Lac, C57BL/6J, DD, and YT) revealed a reliable negative genotypic correlation between hypothalamic maximal specific binding of 3H-clonidine and testosterone level. The detected feedback may be an important regulatory mechanism of the hypothalamo-hypophyseo-gonadal system in male mice.     

Interferon-gamma antagonizes transforming growth factor-beta2-mediated immunosuppression in murine Toxoplasma encephalitis

The in vivo modulating activity of recombinant transforming growth factor (TGF)-beta2 on acute toxoplasmosis was evaluated in both Toxoplasma gondii susceptible C57BL/6 and resistant BALB/c mice. TGF-beta2 lethally exacerbated Toxoplasma encephalitis in C57BL/6, but not in BALB/c mice. In C57BL/6 mice, TGF-beta2 induced a profound dose-dependent increase of the intracerebral parasitic load as well as a reduction of IFN-gamma levels in serum and cerebrospinal fluid with a coincident decrease of MHC class II antigen expression of macrophages, microglial cells, and B cells. Furthermore, TGF-beta2-treated C57BL/6 mice showed a reduced activation of CD4+ and CD8+ T cells and a diminished recruitment of immune cells to the brain. The TGF-beta2-mediated development of lethal toxoplasmosis in C57BL/6 mice was abolished by treatment with recombinant interferon (IFN)-gamma.     

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.     

Differences in the liability to self-administer intravenous cocaine between C57BL/6 x SJL and BALB/cByJ mice

Application of animal models of psychostimulant abuse for experimentation in mice is becoming increasingly important for studying the contribution of genetic differences, as well as the roles of selected (targeted) genes, in specific behaviors. The purpose of this study was to investigate strain differences in cocaine self-administration behavior between C57BL/6 x SJL hybrid mice and BALB/cByJ mice. These two strains were chosen because BALB/cByJ mice have a well-developed behavioral pharmacological profile, and hybrid strains on a C57BL/6 background are commonly used for generating transgenic expressing and knockout mutant mice. C57BL/6 x SJL mice dose-dependently acquired cocaine self-administration (1.0 mg/kg/injection but not 0.25 mg/kg/injection) by responding selectively in the active nose-poke hole and maintaining stable levels of daily drug intake; they also exhibited a characteristic inverted-U-shaped cocaine dose-effect function. BALB/cByJ mice failed to acquire cocaine self-administration at either dose under the same test conditions. The strain differences observed in self-administration did not seem to be attributed to other behavioral differences because the two strains exhibited similar amounts of spontaneous nose-poking in the absence of reinforcers, and BALB/cByJ mice responded more than C57BL/6 x SJL mice in a food-reinforced nose-poke operant task. Importantly, the dose-effect function for the motor stimulating effects of cocaine (3.8-30 mg/kg intraperitoneally) suggests enhanced sensitivity but reduced efficacy of cocaine in stimulating motor activity in BALB/cByJ mice relative to the C57BL/6 x SJL hybrid mice. These results indicate that the decreased liability of BALB/cByJ mice to acquire cocaine self-administration is not the result of differences in spontaneous activity or performance, but may reflect different sensitivities to the reinforcing, or rate-disrupting, properties of cocaine. The data support an influence of genetic background in the liability to self-administer cocaine. Thus, a hypothesis is proposed that the decreased liability of BALB/cByJ mice to acquire cocaine self-administration is related to differences in brain monoamine systems linked to the high "emotionality" profile of BALB/c mice in novel or fearful situations, including perhaps cocaine administration.     

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.     

Voluntary selection of and tolerance to 1,2 propanediol (propylene glycol) by high and low ethanol-selecting mouse strains.

Tested 15 male mice from each of 4 inbred strains (C57BL/6J, BALB/cJ, CBA/J, and DBA/2J) to determine their voluntary self-selection of a 10% solution of 1,2 propanediol (1,2 PD), a 3-carbon alcohol of low toxicity. As with ethanol, the C57BL/6J strain consumed significantly greater amounts than the 3 other low ethanol-selecting strains. Exp II with 140 Ss determined that the 3 low-selecting strains suffered significantly greater depression of the central nervous system from 1,2 PD than the high selecting C57BL strain. It was also found that ethanol was a much more potent depressant than 1,2 PD. Results are discussed in terms of the possible role of neural sensitivity in regulating consumption levels of the 2 alcohols. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ambiguous role of interleukin-12 in Yersinia enterocolitica infection in susceptible and resistant mouse strains

Endogenous interleukin-12 (IL-12) mediates protection against Yersinia enterocolitica in C57BL/6 mice by triggering gamma interferon (IFN-gamma) production in NK and CD4+ T cells. Administration of exogenous IL-12 confers protection against yersiniae in Yersinia-susceptible BALB/c mice but exacerbates yersiniosis in resistant C57BL/6 mice. Therefore, we wanted to dissect the different mechanisms exerted by IL-12 during Yersinia infections by using different models of Yersinia-resistant and -susceptible mice, including resistant C57BL/6 mice, susceptible BALB/c mice, intermediate-susceptible wild-type 129/Sv mice, 129/Sv IFN-gamma-receptor-deficient (IFN-gamma R-/-) mice and C57BL/6 tumor necrosis factor (TNF) receptor p55 chain-deficient (TNFR p55-/-) mice. IFN-gamma R-/- mice turned out to be highly susceptible to infection by Y. enterocolitica compared with IFN-gamma R+/+ mice. Administration of IL-12 was protective in IFN-gamma R+/+ mice but not in IFN-gamma R-/- mice, suggesting that IFN-gamma R-induced mechanisms are essential for IL-12-induced resistance against yersiniae. BALB/c mice could be rendered Yersinia resistant by administration of anti-CD4 antibodies or by administration of IL-12. In contrast, C57BL/6 mice could be rendered more resistant by administration of transforming growth factor beta (TGF-beta). Furthermore, IL-12-triggered toxic effects in C57BL/6 mice were abrogated by coadministration of TGF-beta. While administration of IL-12 alone increased TNF-alpha levels, administration of TGF-beta or TGF-beta plus IL-12 decreased both TNF-alpha and IFN-gamma levels in Yersinia-infected C57BL/6 mice. Moreover, IL-12 did not induce toxicity in Yersinia-infected TNFR p55-/- mice, suggesting that TNF-alpha accounts for IL-12-induced toxicity. Taken together, IL-12 may induce different effector mechanisms in BALB/c and C57BL/6 mice resulting either in protection or exacerbation. These results are important for understanding the critical balance of proinflammatory and regulatory cytokines in bacterial infections which is decisive for beneficial effects of cytokine therapy.     

Surgical treatment of locally advanced rectal cancer. Options and strategies

To evaluate the contribution of the subsets of T helper lymphocyte (Th) to the development of pulmonary lesion in mycoplasma pneumonia, we compared the pathological findings between Th1 dominant mice (C57BL/6) and Th2 dominant mice (BALB/c) in experimental Mycoplasma pulmonis (M. pulmonis) pneumonia. Mice (ICR, C57BL/6, and BALB/c) were intranasally inoculated with 0.03 ml of a solution containing M. pulmonis (1 x 10(8)) colony forming units per ml. Another M. pulmonis inoculated ICR mice were treated with interleukin-2 (IL2; 4.8 micrograms/day), days 3-9, intracutaneously). All mice were sacrificed at day 14, and the lung specimens were examined. Peribronchial lymphocyte cuffing was more prominent in C57BL/6 mice than that of ICR mice, and intra-alveolar inflammatory-cell infiltration in BALB/c mice was more prominent than in ICR mice. Pathological patterns of the lung in IL-2 treated ICR mice were mimicking those of C57BL/6 mice. These results suggested that pathological patterns of mycoplasma pneumonia in mice might be altered by the imbalance of host T helper lymphocyte subset.     

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.     

Prepulse inhibition of the startle response in mice: Relationship to hearing loss and auditory system plasticity.

Prepulse inhibition was used with C57BL/6J (C57) mice to assess behavioral-perceptual correlates of previously demonstrated physiological changes in the central auditory system associated with age-related hearing loss. Normal-hearing CBA/CaJ (CBA) mice and DBA/2J (DBA) mice, which exhibit extremely rapid hearing loss, were also tested. Tone prepulse stimuli (S1s) were presented 100 ms prior to a startle-evoking noise stimulus (S2), and a decrease in startle amplitude served as the measure of startle modification. As high-frequency hearing declined in C57 mice between 1 and 12 mo of age, the efficacy of lower-frequency S1s was significantly enhanced. CBA mice exhibited no age-related changes in startle modification. DBA mice exhibited changes similar to those observed in C57s but at an accelerated rate. The enhanced behavioral saliency of low and middle frequencies in C57 and DBA mice appears to be a consequence of neural plasticity in the central auditory system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Resistance to Leishmania major is linked to the H2 region on chromosome 17 and to chromosome 9

In Leishmaniasis, as in many infectious diseases, clinical manifestations are determined by the interaction between the genetics of the host and of the parasite. Here we describe studies mapping two loci controlling resistance to murine cutaneous leishmaniasis. Mice infected with L. major show marked genetic differences in disease manifestations: BALB/c mice are susceptible, exhibiting enlarging lesions that progress to systemic disease and death, whereas C57BL/6 are resistant, developing small, self-healing lesions. F2 animals from a C57BL/6 X BALB/c cross showed a continuous distribution of lesion score. Quantitative trait loci (QTL) have been mapped after a non-parametric QTL analysis on a genome-wide scan on 199 animals. QTLs identified were confirmed in a second cross of 271 animals. Linkage was confirmed to a chromosome 9 locus (D9Mit67-D9Mit71) and to a region including the H2 locus on chromosome 17. These have been named Imr2 and Imr1, respectively.     

IL-5 is required for eosinophil recruitment, crystal deposition, and mononuclear cell recruitment during a pulmonary Cryptococcus neoformans infection in genetically susceptible mice (C57BL/6)

CBA/J (highly resistant), BALB/c (moderately resistant), and C57BL/6 (susceptible) mice displayed three resistance patterns following intratracheal inoculation of Cryptococcus neoformans 52. The inability to clear the infection correlated with the duration of the eosinophil infiltrate in the lungs. The role of IL-5 in promoting the pulmonary eosinophilia and subsequent inflammatory damage in susceptible C57BL/6 mice was investigated. C57BL/6 mice developed a chronic alveolar, peribronchiolar, and perivascular eosinophilia following C. neoformans infection. This resulted in the accumulation of intracellular Charcot-Leyden-like crystals in alveolar macrophages by wk 4 and the extracellular deposition of these crystals in the bronchioles with associated destruction of airway epithelium by wk 6. IL-5 mRNA was expressed in the lungs, and injections of anti-IL-5 mAb prevented eosinophil recruitment and crystal deposition but did not alter cryptococcal clearance. Depletion of CD4+ T cells (but not CD8+) ablated IL-5 production by lung leukocytes in vitro and eosinophil recruitment in vivo. Neutralization of IL-5 also inhibited the recruitment of macrophages, CD8+ T lymphocytes, and B lymphocytes by 47 to 57%. Anti-IL-5 mAb inhibited CD4+ T lymphocyte recruitment by 30% but did not affect neutrophil recruitment. Thus, the development of a chronic eosinophil infiltrate in the lungs of C. neoformans-infected C57BL/6 mice is a nonprotective immune response that causes significant lung pathology. Furthermore, IL-5 promotes the recruitment and activation of eosinophils, resulting in the recruitment of additional macrophages and lymphocytes into the lungs.     

Suppression of GVH reaction in F1 hybrid mice by foetal liver cells

The effect of foetal liver cells on GVH reaction with the parental lymphocytes in F1 hybrid mice was studied. The GVH reaction was induced in newborn (CBA X C3H)F1 and in 10-day-old (CBA X C57BL/6)F1 hybrid mice. Foetal liver cells did not induce a GVH reaction. The GVH reaction of CBA spleen cells in (CBA X C3H)F1 hybrid mice was demonstrable, although weak. Foetal liver cells suppressed the GVH reaction, in dependence on cell concentration, in (CBA x C3H)F1 but not in (CBA X C57BL/6)F1 hybrid mice. The possibility to induce transplantation tolerance with foetal liver cells is discussed.