Modulation of primary antibody responses to sheep erythrocytes in Plasmodium chabaudi-infected resistant and susceptible mouse strains.

The in vivo primary antibody response to sheep erythrocytes (SRBC) was determined in genetically resistant C57BL/6 and susceptible A/J mice during the course of infection with Plasmodium chabaudi. Spleen cells from both strains of mice, immunized with SRBC and infected on the same day, showed significant increases in the number of direct plaque-forming cells. The response of malaria-infected C57BL/6 mice was significantly enhanced in comparison with the responses of both normal C57BL/6 and malaria-infected A/J mice. When mice were immunized at later times in the infection, the level of the response declined in both strains until it was less than 50% of the response of normal mice. Thus, suppression of the primary antibody response to SRBC does not correlate with the outcome of P. chaubaudi infection in genetically resistant and susceptible hosts.     

Monoclonal antibodies directed against a cell surface-exposed outer membrane protein of Haemophilus influenzae type b.

Strain variation in the level of resistance to malaria was investigated in inbred strains of mice after infection with Plasmodium chabaudi. When infected intraperitoneally with 10(6) P. chabaudi-parasitized erythrocytes, mice of 11 inbred strains could be separated into two groups by using survival time as the criterion; C57BL/6J, C57L/J, DBA/2J, CBA/J, and B10.A/SgSn mice were found to be resistant to P. chabaudi, whereas A/J, DBA/1J, BALB/c, C3H/HeJ, AKR/J, and SJL/J mice were susceptible. An examination of F1 hybrids revealed that resistance was dominant over susceptibility. A segregation analysis of backcross and F2 progeny derived from susceptible A/J and resistant B10.A/SgSn parental mice suggested that host resistance in this strain combination was genetically controlled by a single, dominant, non-H-2-linked gene. Inheritance of resistance was autosomal, but expression of the trait was influenced by the sex of the host, female mice being more resistant than male mice. Phenotypic expression of the resistance gene was apparent within 6 days of infection as a significant difference between resistant and susceptible mice in the level of parasitemia. A preliminary analysis of the mechanism of resistance showed that compared with susceptible A/J mice, resistant B10.A/SgSn hosts had an augmented erythropoietic response during the course of malaria, as well as phenylhydrazine-induced anemia. These results suggest that the ability to replace destroyed erythrocytes quickly and efficiently may determine host survival after infection with P. chabaudi.     

Genetic control of susceptibility to infection with Plasmodium chabaudi chabaudi AS in inbred mouse strains

To identify genetic effects modulating the blood stage replication of the malarial parasite, we phenotyped a group of 25 inbred mouse strains for susceptibility to Plasmodium chabaudi chabaudi AS infection (peak parasitemia, survival). A broad spectrum of responses was observed, with strains such as C57BL/6J being the most resistant (low parasitemia, 100% survival) and strains such as NZW/LacJ and C3HeB/FeJ being extremely susceptible (very high parasitemia and uniform lethality). A number of strains showed intermediate phenotypes and gender-specific effects, suggestive of rich genetic diversity in response to malaria in inbred strains. An F2 progeny was generated from SM/J (susceptible) and C57BL/6J (resistant) parental strains, and was phenotyped for susceptibility to P. chabaudi chabaudi AS. A whole-genome scan in these animals identified the Char1 locus (LOD=7.40) on chromosome 9 as a key regulator of parasite density and pointed to a conserved 0.4-Mb haplotype at Char1 that segregates with susceptibility/resistance to infection. In addition, a second locus was detected in [SM/J × C57BL/6J] F2 mice on the X chromosome (LOD=4.26), which was given the temporary designation Char11. These studies identify a conserved role of Char1 in regulating response to malaria in inbred mouse strains, and provide a prioritized 0.4-Mb interval for the search of positional candidates.     

Host defenses in experimental rickettsialpox: genetics of natural resistance to infection.

The genetic basis for natural resistance to lethal infection with Rickettsia akari was studied in over 25 inbred strains, inbred hybrids, and outbred stocks of mice. Inbred mice infected intraperitoneally with the Kaplan strain of R. akari demonstrated three levels of response, susceptible (C3H/HeJ), intermediate (A/HeJ, A/J, A/WySn, BALB/cDub, BALB/cJ, and SJL/J), and resistant (AKR/J, AL/N, BALB/cAnN, BALB/cNCr1BR, C3H/HeN, C57BL/6J, C57L/J, CBA/J, DBA/2J, and SWR/J). No correlation was evident between the six H-2 haplo-types tested and susceptibility to Kaplan infection. Four outbred mouse stocks, Dub: (ICR), Wrc:(ICR), Caw:(CF1), and Mai:(S) were all resistant. The F1 inbred hybrids of resistant X resistant (AKD2F1/J), resistant X intermediate (CB6F1/U), intermediate X intermediate (CAF1/J), and resistant X susceptible (C3D2F1/J) parents were all resistant. The F2 and parental backcross generations of C3H/HeJ and DBA/2J hybrids yielded ratios of resistant to susceptible mice that suggested resistance was under multigeneic control. Susceptible mice (C3H/HeJ) were capable of mounting an immune response, since prior infection with the avirulent Hartford strain of R. akari rendered them resistant to subsequent lethal challenge with the Kaplan strains.     

Genetic control of susceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice

The importance of host factors in determining susceptibility to systemic Candida albicans infections is evident in both humans and mice. We have used a mouse model to study the genetic basis of susceptibility, using the inbred strains A/J and C57BL/6J, which are susceptible and resistant, respectively, based on different parameters of the response to infection. To identify genes responsible for this differential host response, brain and kidney fungal load were measured in 128 [A/J x C57BL/6J] F(2) mice 48 h after infection with 5 x 10(4) C. albicans blastospores. Segregation analysis in this informative population identified complement component 5 (C5/Hc) as the major gene responsible for this differential susceptibility (LOD of 22.7 for kidney, 19.0 for brain), with a naturally occurring mutation that causes C5 deficiency leading to enhanced susceptibility. C5 was also found to control heart fungal load, survival time, and serum TNF-alpha levels during infection. Investigation of the response to C. albicans challenge in a series of AcB/BcA recombinant congenic strains validated the importance of C5 in determining the host response. However, the strains BcA67 and BcA72 showed discordant phenotypes with respect to their C5 status, suggesting additional complexity in the genetic control of the inter-strain difference in susceptibility observed in A/J and C57BL/6J following systemic infection with C. albicans.     

Host Defenses in Experimental Scrub Typhus: Genetics of Natural Resistance to Infection

Genetic resistance to lethal infection with Rickettsia tsutsugamushi was studied in over 30 inbred strains, inbred hybrids, and outbred stocks of mice. Inbred mice infected intraperitoneally with the Gilliam strain of R. tsutsugamushi showed three patterns of response: susceptible (A/HeJ, C3H/HeDub, C3H/HeJ, C3H/HeN, C3H/St, CBA/J, DBA/1J, DBA/2J, and SJL/J), resistant (AKR/J, BALB/cDub, BALB/cJ, C57BL/6J, C57L/J, and SWR/J), and selectively resistant (A/J). The selectively resistant pattern was characterized by random deaths occurring throughout the titration range and was also observed in three of the six outbred mouse stocks surveyed. No correlation was evident between the H-2 haplotype of inbred mice and their response to Gilliam infection. The progeny from five different Gilliam-resistant by Gilliam-susceptible inbred parental crosses were all resistant. Study of F(1), F(2), and parental backcross generations of BALB/cDub (resistant) and C3H/HeDub (susceptible) hybrids indicated resistance was dominant and was controlled by a single gene or a closely linked cluster of genes that were autosomal and not linked to coat color. The resistance of BALB/cDub mice was not due to an inability of host cells to support rickettsial growth, since C3H/HeDub and BALB/cDub embryo cell cultures supported similar growth of Gilliam organisms. C3H/HeDub mice, although susceptible to intraperitoneal Gilliam infection, were capable of mounting an immune response to Gilliam antigens, since subcutaneous infection was not lethal and did protect animals against subsequent intraperitoneal challenge with either the Gilliam or Karp strains of R. tsutsugamushi.     

Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. II. Survey of host immune responses and central nervous system virus titers in inbred mouse strains

Previous studies using mouse strains with limited genetic differences and H-2 haplotypes demonstrated that susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease strongly correlated with chronically high levels of TMEV-specific delayed-type hypersensitivity (DTH), but not with TMEV-specific T cell proliferation (Tprlf), serum antibody responses, or with CNS virus titers. To determine if this correlation would be supported by analysis of these parameters in a more thorough genetic survey, ten inbred mouse strains, representing a wide variety of genetic backgrounds and H-2 haplotypes, were inoculated intracerebrally (i.c.) with the BeAn strain of TMEV. Significant TMEV-specific DTH was observed in all highly susceptible strains, but was not detectable in intermediate and resistant strains. TMEV-specific serum antibody titers also appeared to correlate with susceptibility to demyelinating disease, however even resistant strains had high antibody responses. Significant differences in CNS TMEV titers existed between strains, but did not correlate with disease susceptibility. DTH and Tprlf responses were observed in 3/4 resistant strains following peripheral immunization with UV-inactivated TMEV indicating that most resistant strains are genetically capable of mounting virus-specific cell-mediated immune (CMI) responses. The data extends our knowledge of host immune responses and virus titers in many different inbred mouse strains persistently infected with TMEV, supports the hypothesis that the demyelination in highly susceptible mice involves a TMEV-specific DTH response, and suggests that the genetic ability to mount specific DTH responses is necessary, but not sufficient for development of the demyelinating disease.     

Influence of the genetic pattern and sex of mice in experimental paracoccidioidomycosis

Eight genetically different strains of mice were compared regarding the dissemination of Paracoccidioides brasiliensis to the lungs, liver and omentum/pancreas, DTH responses and specific antibody production at 16 weeks after intraperitoneal infection with Pb18, a virulent P. brasiliensis isolate. The degree of dissemination of the infection varied: B10.A and C57Bl/6, the most susceptible mouse strains, had positive cultures and high colony-forming unit (CFU) counts in all analysed organs. DBA/2 and A/Sn mice had negative cultures, being thus classified as the most resistant strains. CBA/J, C3H/HeJ, F₁(A/SnxB10.A) and BALB/c mice were regarded as relatively resistant, since discrete fungal growth was observed only in one or two of the studied organs. All mouse strains, except B10.A mice, produced specific DTH responses which did not seem to be associated with the severity of disease. Production of high levels of specific antibodies was found in all strains except in the DBA/2 and C57B1/6 mice. The influence of the host sex on the outcome of paracoccidioidomycosis was evident only in susceptible animals: female B10.A mice displayed lower CFU counts in the three examined organs, whereas no differences were found between male and female A Sn animals. The higher resistance of female B10.A mice was not accompanied by differences in their capacity to maintain a DTH reaction, nor in their production of antibody. This fact argues against the widely believed association of susceptibility to P. brasiliensis infection with both impaired DTH reactivity and increased humoral response.     

Host response to infection with a temperature-sensitive mutant of Salmonella typhimurium in a susceptible and a resistant strain of mice.

The inoculation of a temperature-sensitive mutant of Salmonella typhimurium induced a long-lasting infection in susceptible (C57BL/6) and resistant (A/J) mice. During week 1 of infection, the number of bacteria in the spleens was similar in both mouse strains. Then, the decrease of bacteria was more rapid in the resistant strain. Splenomegaly and granulomatous hepatitis were more severe in the susceptible strain. The immune response induced by this infection was studied. In both mouse strains delayed-type hypersensitivity to Salmonella antigens was present, and resistance to reinfection with a virulent strain of S. typhimurium or with Listeria monocytogenes appeared with the same kinetics. Thus, it does not seem that the gene(s) controlling natural resistance to S. typhimurium act(s) on acquired immunity.     

Genetic control of resistance to Salmonella typhimurium infection in high and low antibody responder mice.

Mice selected by Biozzi for high and low responses to sheep erythrocytes were investigated for resistance to subcutaneous Salmonella typhimurium infection. The resistance was measured by LD50 values, viable bacterial counts in liver and spleen at 10 days, and the kinetics of infection over 4 weeks. High responder mice were susceptible to S. typhimurium injected subcutaneously (LD50 less than 10) and low line resistant (LD50 3 x 10(6)). Control of natural resistance to S. typhimurium in inbred mice is primarily by a single gene. Ity, on chromosome 1. Results with hybrid generations of Biozzi mice with either BALB/c (sensitive) or CBA (resistant) inbred mice indicated additional genetic control of resistance in Biozzi mice. Analysis of resistance data of backcrosses of (high x low)F1 with either parental strain showed this genetic control to be at least one other gene in the Biozzi mice, not linked to Ity. The antibody responses in the hybrid generations and inbred and Biozzi parental strains were tested by haemagglutination assays and ELISA. After specific stimulation of the mice there was an inverse relationship between resistance to S. typhimurium and antibody levels.     

IgG subclass responses to Theiler's murine encephalomyelitis virus infection and immunization suggest a dominant role for Th1 cells in susceptible mouse strains.

Inbred mouse strains differ in susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. A strong correlation between disease susceptibility and delayed-type hypersensitivity (DTH) has been previously demonstrated, but no strong correlation between disease susceptibility and total anti-TMEV ELISA titres was shown. Since both DTH and IgG2a antibody production are regulated by CD4+ Th1 cells, we investigated three strains of mice to determine whether antivirus IgG2a antibody levels, like DTH in previous studies, correlated with disease susceptibility. Susceptible SJL/J, intermediately susceptible C3H/HeJ, and resistant C57BL/6 mice were infected intracerebrally (i.c.) with the BeAn strain of TMEV and monitored for clinical signs of demyelination and for levels of TMEV-specific antibody of different IgG subclasses using a particle concentration fluorescence immunoassay (PCFIA). Resistant C57BL/6 mice were found to have significantly lower concentrations of total anti-TMEV antibody than susceptible SJL/J mice and intermediately susceptible C3H/HeJ mice show variable antibody responses. A predominance of anti-TMEV IgG2a (Th1 regulated) antibody was seen in susceptible and intermediately susceptible mice, whereas resistant mice displayed a predominant anti-TMEV IgG1 (Th2 regulated) response accompanied by a marked deficiency of IgG2a. In contrast, immunization of C57BL/6 mice with UV-inactivated TMEV in adjuvant revealed that this strain was not defective either in its ability to generate high levels of anti-TMEV antibody or in its ability to produce IgG2a antibody. These results suggest that the antivirus IgG subclass profile is dependent upon the immunization route, virus viability and/or the use of adjuvant and that the levels of antivirus subclasses may be predictive of disease susceptibility.     

Genetic susceptibility to vaginal candidiasis.

To enable future studies on host resistance factors and therapy, inbred and outbred mouse strains were tested for susceptibility to vaginal candidiasis. Groups of mice were given 0.5 mg estradiol 3 days before and 4 days after intravaginal challenge with a suspension of Candida albicans. On day 1 after challenge, a swab was used to quantitate infection in all groups and to assure equivalent infection levels. On day 6, this was repeated and the experiment was terminated. BALB/c, the reference strain in repeated experiments, was susceptible, showing persistent infection with levels of cfu at day 6 falling within a range between a twofold decrease and a fourfold increase in relation to day 1 levels. CD-1 outbred mice were markedly resistant, with day 6 cfu levels showing a 74- to 87-fold decrease with respect to day 1 levels, whereas other outbred strains (CF-1, SW, ICR) were susceptible. A BALB/c substrain (ByJ) was also susceptible. With exception of CBA/J, which showed modest resistance, all inbred strains were similarly susceptible, including DBA/2, AKR/J, C3H/HeN, A/J and C57BL/6. The differences between CD-1 and BALB/c mice were also seen with a second C. albicans isolate. Our results show susceptibility to vaginal candidiasis is independent of the major histocompatibility locus H2 haplotype and any effect ascribable to use of particular commercial mouse suppliers. Differences among mouse strains in susceptibility to C. albicans, as seen in previous studies involving nonvaginal challenge routes, are not reflected in this vaginal candidiasis model; in general, such resistance patterns appear specific to the route of challenge administration. The resistance seen in mouse strain CD-1 is of particular interest in that CD-1 is known to be resistant to endocrine disruption by estrogen. Our results suggest this estrogen insensitivity may have broad-ranging effects on processes other than gametogenesis, including vaginal susceptibility to candidiasis.     

Multigenic control and sex bias in host susceptibility to spore-induced pulmonary anthrax in mice

Mechanisms underlying susceptibility to anthrax infection are unknown. Using a phylogenetically diverse panel of inbred mice and spores of Bacillus anthracis Ames, we investigated host susceptibility to pulmonary anthrax. Susceptibility profiles for survival time and organ pathogen load differed across strains, indicating distinct genetic controls. Tissue infection kinetics analysis showed greater systemic dissemination in susceptible DBA/2J (D) mice but a higher terminal bacterial load in resistant BALB/cJ (C) mice. Interestingly, the most resistant strains, C and C57BL/6J (B), demonstrated a sex bias for susceptibility. For example, BALB/cJ females had a significantly higher survival time and required 4-fold more spores for 100% mortality compared to BALB/cJ males. To identify genetic regions associated with differential susceptibility, survival time and extent of organ infection were assessed using mice derived from two susceptibility models: (i) BXD advanced recombinant inbred strains and (ii) F2 offspring generated from polar responding C and D strains. Genome-wide analysis of BXD strain survival identified linkage on chromosomes 5, 6, 9, 11, and 14. Quantitative trait locus (QTL) analysis of the C×DF2 population revealed a significant QTL (designated Rpai1 for resistance to pulmonary anthrax infection, locus 1) for survival time on chromosome 17 and also identified a chromosome 11 locus for lung pathogen burden. The striking difference between genome-wide linkage profiles for these two mouse models of anthrax susceptibility supports our hypothesis that these are multigenic traits. Our data provide the first evidence for a differential sex response to anthrax resistance and further highlight the unlikelihood of a single common genetic contribution for this response across strains.     

Genetic control of in vitro natural cell-mediated activity against Salmonella typhimurium by intestinal and splenic lymphoid cells in mice.

In vitro natural anti-bacterial activity against Salmonella typhimurium by lymphocytes from Peyer's patches and spleens was assessed in several mouse strains. C3H/HeN and CBA/J mice, which are resistant to S. typhimurium infections, showed a natural anti-bacterial activity significantly higher than BALB/c, C57BL/10, C57BL/6 and C3H/HeJ mice, i.e. strains susceptible to the in vivo bacterial infection. In these susceptible strains and also in A/J mice, a significantly higher natural activity was observed in females compared to males. The sex control of natural anti-bacterial activity was further stressed by the fact that orchidectomy could induce a strong activity in low responder C57BL/10 male mice. With the exception of Beige mice, a low natural killer (NK) strain also with no natural activity against S. typhimurium in both sexes, the genetic distribution of natural anti-bacterial activity was extremely different from that of the NK activity. Thus, these results further stress the difference between natural anti-bacterial activity and NK cytotoxicity. Furthermore, our data establish a possible link, although with some exceptions, between in vivo susceptibility to S. typhimurium infections and in vitro natural activity against these bacteria.     

Genetic control of murine listeriosis expressed in the macrophage response

Susceptibility to murine listeriosis is genetically regulated. For example, A/J, C3H, CBA, DBA/1, DBA/2 and 129/J mouse strains are classed as susceptible and demonstrate an early net bacterial growth rate which is significantly higher than that seen in strains classed as resistant, namely, C57BL-derived strains, NZB and SJL. These strain differences in susceptibility are expressed during the phase of natural resistance, as a property of the macrophage response. Genetic analysis in progeny derived from resistant C57BL-derived strains and susceptible A/J or BALB/c strain mice has indicated that a major gene is responsible for determining resistance/susceptibility to listeria. The genetic advantage of the resistant phenotype is attributed to a prompt influx of young (radiosensitive) inflammatory macrophages which control the early bacterial multiplication in infective sites. Such cells reportedly have superior listericidal activity in vitro, as compared to mature macrophages. Mononuclear phagocyte production, emigration and accumulation at infective foci are all increased in resistant C57BL, but not in susceptible A/J mice, shortly following infection. Thus, resistance to listeriosis is associated with an efficient macrophage inflammatory response and, conversely, susceptibility is attributed to a sluggish response. Genetic studies have demonstrated linkage between these two traits (listeria resistance/susceptibility and the macrophage inflammatory response). In all probability, different gene loci are responsible for susceptibility amongst the various mouse strains. In A/J mice, susceptibility is attributed to C5 deficiency (specified by Hc locus) while, for C5-sufficient strains, another genetic defect is presumably responsible.(ABSTRACT TRUNCATED AT 250 WORDS)     

Strain-Dependent Differences in Murine Susceptibility to Coccidia

Differences in susceptibility of strains of mice to Eimeria ferrisi were observed by infecting eight strains of mice with six infectious dose levels and comparing the mortality rate among the strains for a period of 12 days. Mice of the C57BL/6 and HA/ICR strains were susceptible, and those of A/He, AKR, BALB/c, CBA, C3H/Anf, and DBA/2 strains were resistant to coccidial infection. Resistance was a dominant genetic expression, as indicated by the resistant response of F(1) hybrids of susceptible C57BL/6 and resistant CBA, C3H/Anf, or DBA/2 strains. An E. ferrisi infection in congenitally athymic nu/nu mice and phenotypically normal heterozygous nu/+ mice was used to determine how thymus-dependent immunoincompetence in cell-mediated immunity of the nu/nu mouse affected resistance to infection in a genetic background of the resistant BALB/c mouse. Results of primary and challenge infections in these two strains of mice suggested that resistance is thymus dependent. Furthermore, impairment of thymus-dependent cell-mediated immunity in resistant AKR mice by treatment with mouse antithymus serum led to partial susceptibility. However, susceptible C57BL/6 and HA/ICR strains are phenotypically normal mice, and previous evidence showed that C57BL/6 mice are not completely immunoincompetent in cell-mediated reactivity to coccidia. Collectively, our data show that cell-mediated immunity is necessary for resistance but may be subjected to modification by genetic expression of the host. The possible role of immune response genes in the control of coccidial immunity is discussed.     

Susceptibility of inbred strains of mice to Trypanosoma congolense: correlation with changes in spleen lymphocyte populations.

A comparison was made of the susceptibility of eight inbred strains of mice to infection with Trypanosoma congolense. Marked differences in susceptibility as judged by survival were found between the different strains. The capacity of certain strains to survive longer than others appeared to be related to their ability to limit the numbers of trypanosomes in the circulation. There was no difference in the infectivity of T. congolense for mice of high and low susceptibility. Furthermore, the findings of similar prepatent periods suggested that the initial replication rate was similar in the different strains. These findings suggested that the level of parasitaemia in different strains of may reflect differences in the nature of quality of the immune response to the trypanosome. In all of the strains of mice a marked increase in splenic B and null lymphocytes was found. This, allied to the finding of an increase in the background plaque-forming cells to sheep erythrocytes, indicated, as suggested by other workers, that trypanosome infection results in a non-specific polyclonal activation of lymphocytes, and that this affects primarily B lymphocytes. In strains of mice which survived longest, i.e. C57B1/6J and AKR/A, the increase in splenic B and null cells was less marked. Whether this is associated with a decreased susceptibility of these strains to polyclonal activation induced by trypanosome infection, or whether it is merely the result of lower levels of parasitaemia, remains to be determined. By comparing T. congolense infection in three strains of mice congenic at the H-2 locus, representing H-2a, H-2b and H-2k haplotypes, it was found that the susceptibility was not associated with the H-2 haplotype. The finding that (A/J X C57B1/6J)F1 hybrids were of similar susceptibility as the C57B1/6J parents indicated that the relative resistance of this strain is inherited as a dominant trait, although in the early stages of infection the F1 hybrids consistently showed somewhat higher levels of parasitaemia than the C57B1/6J mice. Athymic nude mice and surgically splenectomized mice were found to be more susceptible to T. congolense infection than intact mice of the same strain. However, the effect of splenectomy was much less pronounced in C57B1/6J mice than in the relatively more susceptible BALB/c/A mice.     

Contrasuppressor cells induced by Junin virus.

Intracerebral inoculation of Junin virus (JV) in all susceptible mouse models available induces a lethal meningoencephalitis compatible with a delayed-type hypersensitivity (DTH) immune response. In contrast, adult BALB/c mice prove resistant to infection and no DTH response is seen. JV inoculation in adult BALB/c mice induces DTH suppression to unrelated antigens such as sheep red blood cells. (SRBC). This suppression is mediated by JV-induced T cells (Tsv), which are operative from 1 to 24 days post-infection (p.i.), and seems to be related to adult mouse survival. The presence of JV-induced contrasuppressor cells (CS) bearing the Thy-1+, Ly 1+2- phenotype, able to abrogate Tsv cells-mediated suppression, is described here. Thus, CS cells may be involved in the mechanism by which mice avoid over-exposure to Tsv-mediated DTH suppression. Such CS cells were found in the spleen of inoculated animals and may also be induced by transferring JV-free Tsv cells to 'naive' recipients, in which JV inoculation then induces morbidity.     

Murine susceptibility to Chagas' disease maps to chromosomes 5 and 17

Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and commonly modelled in inbred mice. Susceptibility of mouse strains to experimental infection varies considerably. We quantified parasite tissue burdens in resistant and susceptible strains by real time PCR and applied a backcross strategy to map the genomic loci linked to susceptibility in inbred mice. Resistant B6D2F1 mice were backcrossed with susceptible C57BL/6 mice, and 46 of a total 192 offspring died after infection. Their genomes were scanned with microsatellite markers. One region on chromosome 17 was significantly linked to susceptibility, while another on chromosome 5 was suggestive of linkage.