Neospora caninum: high susceptibility to the parasite in C57BL/10ScCr mice

C57BL/10ScCr mice, lack Toll-like receptor 4 and a functional Interleukin-12 receptor. Taking this into account, susceptibility of these mice to Neospora caninum infection was assessed comparatively to that of immunocompetent C57BL/10ScSn mice. C57BL/10ScCr mice inoculated intraperitoneally with 5x10(5)N. caninum tachyzoites showed a high susceptibility to this parasite. All infected C57BL/10ScCr mice were dead by day 8 post-infection whereas all control C57BL/10ScSn mice survived this parasitic challenge. Immunohistochemical analysis of infected C57BL/10ScCr mice showed N. caninum tachyzoites spread in the pancreas, liver, lung, intestine, heart and brain whereas no parasites were detected in similarly infected C57BL/10ScSn controls. The higher susceptibility of C57BL/10ScCr mice to neosporosis correlates with reduced interferon-gamma mRNA expression and increased IL-4 mRNA expression, comparatively to C57BL/10ScSn controls, detected in the spleen after the parasitic challenge. C57BL/10ScCr mice could thus be used as a new experimental model where to study immunobiological mechanisms associated with host susceptibility to neosporosis.     

Early influx of Listeria-reactive T lymphocytes in liver of mice genetically resistant to listeriosis

Murine listeriosis is a classical model for investigating mechanisms of cellular immunity, which involves interaction of macrophages and T lymphocytes. The early course of this experimental infection is under control of a limited number of genes in the murine host. In the present study, we asked whether the early efficient control of bacterial growth in the liver of resistant mice is related to the expression of a more rapid specific immune response in this organ than in susceptible mice. Therefore, we compared the frequencies of Listeria monocytogenes-reactive T cells in blood, spleen, and liver of resistant C57BL/6 and susceptible C3H/He Past mice after i.v. injection of a high dose of Listeria (9 x 10(5) CFU). T cells were titrated through their ability to locally transfer a delayed-type hypersensitivity reaction to viable L. monocytogenes, an effector function potentially relevant to the early step of protective mechanisms. We observed (1) a 9- and 4-fold increase by day 1 in the frequency of Listeria-reactive transfer units in the blood of C57BL/6 and C3H mice, respectively, (2) no increase in the number of Listeria-reactive transfer units in the spleen of 2-day infected mice of both strains, and (3) a 90-fold increase, at day 2, in the number of Listeria-reactive transfer units in the liver of resistant C57BL/6 compared with only a 9-fold increase in the liver of susceptible C3H/He. These results suggest that the ability of C57BL/6 mice to control the early bacterial growth (0 to 48 h) in their liver, may be related to a rapid influx of L. monocytogenes-reactive T lymphocytes.     

Genetics of resistance to the African trypanosomes. IV. Resistance of radiation chimeras to Trypanosoma rhodesiense infection

The cellular bases of resistance to the African trypanosomes were examined in inbred mice. As part of these studies, reciprocal bone marrow cell transplants were performed between H-2 compatible mice which differ in relative resistance to Trypanosoma brucei rhodesiense infection. Survival times, parasitemias and IgM antibody responses to the surface antigen of the infecting variant type were measured in these semiallogeneic bone marrow chimeras. Relatively resistant C57BL/10 mice, intermediate A.By mice, and least resistant C3H.SW mice that were reconstituted after lethal irradiation with syngeneic bone marrow cells displayed resistance and immunity characteristic of the homologous donor strain. When C57BL/10 mice were reconstituted with C3H.SW mouse bone marrow cells they retained the ability to produce antibodies to trypanosome surface antigen but the antibody titers were significantly reduced. Control of parasitemia and mean survival time were reduced in these chimeras, but differed significantly from C3H.SW mice. A.By mice that received cells from C57BL/10 donors exhibited antibody responses and survival times similar to the C57BL/10 mice. Survival times of A.By mice given syngeneic cells or C3H.SW cells were the same, but the antibody responses of A.By mice given C3H.SW cells were lower than those of A.By mice given syngeneic cells. C3H.SW mice reconstituted with C57BL/10 bone marrow cells were capable of making antibodies and controlling parasitemia, in marked contrast to the absence of such responses in C3H.SW mice reconstituted with syngeneic cells. Survival times, however, were indistinguishable from those of C3H.SW mice given syngeneic cells. Thus, resistance to T. b. rhodesiense was shown for the first time to depend on donor bone marrow derived cells as well as upon radiation-resistant cells/factors associated with host genetic background. Also, parasite-specific IgM antibody responses seem to be regulated by a mechanism which does not depend on bone marrow derived cells alone, and the presence of such immune responses is not linked to survival time.     

The in vitro bactericidal activity of peritoneal and spleen cells from Listeria-resistant and -susceptible mouse strains

Two days after Listeria-resistant (LrR) C57BL/10 mice were infected intraperitoneally with Listeria, their peritoneal macrophages demonstrated enhanced bactericidal activity beyond that seen in susceptible (LrS) BALB/c or CBA mice. Intravenous infection had no effect on peritoneal cell activity. The induction, but not expression, of the enhanced activity was radiosensitive. There was no significant difference between the strains with respect to the number of cells or cellular composition of the exudates. No difference in the in vitro chemotactic response of cells from the two strains could be demonstrated. Therefore there seems to be recruitment to the infected peritoneal cavity of C57BL/10 mice of young, efficiently bactericidal monocytes/macrophages. On the other hand, spleen cell bactericidal activity was intrinsically superior in C57BL/10 mice compared with BALB/c mice, possibly because, as a haemopoietic organ, the C57BL/10 spleen already contains high numbers of these efficient monocytes.     

Immune control of Brucella abortus 2308 infections in BALB/c mice

BALB/c mice infected with Brucella abortus strain 2308 have 10-fold higher levels of bacteria during the plateau phase of infection (the time period when the number of colony-forming units in vivo remains consistent) than the more resistant C57BL/10 mice. This is due to a cessation of interferon-gamma (IFN-gamma) production that begins after the first week of infection and continues until the end of the plateau phase at least 6 weeks post infection. Despite the lack of IFN-gamma production during this time BALB/c mice are able to prevent an increase in bacterial colony-forming units. Here it was shown that both tumor necrosis factor (TNF)-alpha and CD8 T cells were involved in controlling bacterial numbers in BALB/c mice during this time. That is, neutralization of TNF-alpha or depletion of CD8 T cells with monoclonal antibodies resulted in a significant increase in the number of splenic colony-forming units recovered at 3 weeks post infection. In the absence of CD8 T cells there was also a significant increase in splenic macrophages. The role of TNF-alpha may depend upon the presence of interferon-gamma early in the infection since when TNF-alpha was neutralized in interferon-gamma gene knockout mice there was a marked increase in splenic macrophages, NK cells and neutrophils but not a significant increase in colony-forming units.     

Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. II. Pathogenesis

The pathogenesis of mousepox due to infection with ectromelia virus strain NIH-79 was characterized in genetically susceptible (BALB/cAnNCr) and genetically resistant (C57BL/6NCr) mice. BALB/c mice inoculated subcutaneous (s.c.) or intranasally (i.n.) had high mortality. Most mice died within 7 days from severe necrosis of the spleen and liver. Necrotic foci in livers of BALB/c mice that survived beyond 7 days often were accompanied by mononuclear cell infiltrates and by hyperplasia of lymphoid tissues. C57BL/6 mice inoculated by either route remained asymptomatic and necrotic lesions were mild or absent, whereas focal non-suppurative hepatitis and lymphoid hyperplasia were prominent. Infectious virus and viral antigen were distributed widely in tissues of BALB/c mice, but had limited distribution in C57BL/6 mice. Both mouse strains had infection of the respiratory tract, genital tract, oral tissues and bone marrow, and BALB/c mice also had infection of the intestines. Both strains also developed serum antibody to vaccinia virus antigen after infection. The results show that ectromelia virus occurs in tissues conducive to mouse to mouse transmission and that the severity and character of mousepox lesions correlate directly with resistance and susceptibility to infection. They also support the concept that cellular immunity contributes to survival from infection.     

INFLUENCE OF AGE AND ANTIGENIC STIMULATION ON GRANULOCYTE AND MACROPHAGE PROGENITOR CELLS IN THE MOUSE SPLEEN

The frequency and proliferative activity of granulocytic and macrophage progenitor cells were determined in the spleens of C₅₇BL, BALD/c, NZB and CBA mice. These cells were detected by their capacity to form granulocytic and/or macrophage colonies ( in vitro colony-forming cells, CFC) in agar culture. In vitro CFCs were low in frequency in the adult spleen (4–28/10⁵ cells) compared with the bone marrow (180–280/10⁵ cells). However, the neonatal spleen, both in germfree and conventional mice, contained high levels of in vitro CFCs. From the low suiciding index with tritiated thymidine and the small numbers of cluster-forming cells in relation to colony numbers, many in vitro CFCs in the adult C₅₇BL spleen appear to be in a non-cycling state. The level and activity of in vitro CFCs were extremely low in the spleen of adult germfree CBA mice but were greatly increased in conventional mice following the injection of a bacterial antigen.     

Murine cytomegalovirus infection can enhance hybrid resistance through modulation of host natural killer activity

Studies were undertaken to assess the effect of murine cytomegalovirus (MCMV) in two different models involving injection of parental cells into F1 hosts. In both of these systems, MCMV-induced enhancement of hybrid resistance was found. In the first model, parent-into-F1 graft-vs-host reaction, MCMV infection of (C57BL/6 x C3H)F1 (B6C3F1) hosts was found to prevent the GVHR normally induced by injection of B6 parental splenocytes into the F1 hosts. The second model involved injection of parental bone marrow into lethally irradiated B6C3F1 and (C57BL/6 x DBA/2)F1 (B6D2F1) hosts. These irradiated hosts are known to exhibit resistance to engraftment by parental C57BL/6 (B6) bone marrow. This resistance was found to be markedly enhanced by injection of the hosts with MCMV 3 days before irradiation and bone marrow injection. In contrast, engraftment into B6C3F1 hosts of syngeneic marrow, or bone marrow from the C3H parent, was not affected by MCMV infection. Engraftment of DBA/2 marrow into B6D2F1 hosts was reduced at lower doses of injected marrow, suggesting enhanced resistance against the minor Hh Ag Hh-DBA. To test whether the MCMV-induced enhancement of resistance was mediated by NK cells, splenic NK activity (YAC-1 killing) and frequency (NK1.1 staining) were assessed. Both parameters were found to be elevated at 3 days after MCMV infection but to return to normal levels by 9 days. B6 bone marrow engraftment was in fact found to be normal when the marrow was administered to F1 mice 9 days after MCMV infection. Furthermore, anti-asialoGM1 administration prevented MCMV-induced enhancement of resistance to marrow engraftment. Thus, the NK enhancement resulting from MCMV infection appears to play a major role in the enhanced HR observed in the marrow engraftment model. This effect may be of importance in clinical bone marrow transplantation, a situation in which patients are susceptible to viral infection.     

Differences in initial rate of intracellular killing of Salmonella typhimurium by resident peritoneal macrophages from various mouse strains

To determine the underlining mechanism of the difference in innate susceptibility of mouse strains to infection by Salmonella typhimurium, the ingestion and in vitro intracellular killing of S. typhimurium by resident peritoneal macrophages of mouse strains that differ in natural resistance to this microorganism has been studied. The results revealed that the rate constants of in vitro phagocytosis (Kph) in the presence of inactivated rabbit immune serum did not differ between macrophages of susceptible C57BL/10 and resistant CBA mice (for both strains: Kph = 0.021 min-1). The rate constant of in vitro intracellular killing (Kk) was determined 1) after in vivo phagocytosis (CBA, Kk = 0.055 min-1; C57BL/10, Kk = 0.031 min-1), 2) after in vitro phagocytosis of preopsonized bacteria (CBA, Kk = 0.020 min-1; C57BL/10, Kk = 0.012 min-1), and 3) during continuous phagocytosis in vitro (CBA, Kk = 0.029 min-1; C57BL/10, Kk = 0.013 min-1). With all three approaches, the initial rate of intracellular killing by normal macrophages of Salmonella-resistant CBA mice amounted to about 1.7 times the value found for macrophages of susceptible C57BL/10 mice (p less than 0.01). This trait difference was independent of the previous way of ingestion of the bacteria, unaffected by the kind of opsonization, and specific for S. typhimurium, because Staphylococcus aureus and Listeria monocytogenes were killed by macrophages of these mouse strains with equal efficiency (p greater than 0.50). These findings indicate that a difference in genetic background expressed in the efficacy of intracellular killing by resident peritoneal macrophages immediately upon ingestion of S. typhimurium is relevant for the innate resistance of mice against S. typhimurium.     

Role of natural killer cells as immune effectors in encephalitis and demyelination induced by Theiler's virus

Infection of susceptible mice (SJL) with Theiler's murine encephalitis virus (TMEV) causes a biphasic disease characterized by gray matter inflammation followed by late chronic demyelination. The role of NK cells was studied in this model by using susceptible (SJL) or resistant (C57BL/10) mice. CNS TMEV titer were higher in SJL compared with C57BL/10 mice, correlating with a 50% lower NK cell activity in the SJL than in the C57BL/10 mice. When resistant (C57BL/10) mice were depleted of NK cells using either mAb NK1.1 or polyclonal anti-asialo-GM1, TMEV induced the development of diffuse encephalitis and meningitis early in the postinfection period (days 6 to 11). However, the second phase of TMEV-induced CNS disease (demyelination) was observed only in resistant C57BL/10 mice treated with anti-asialo-GM1. Experiments with beige/beige mice of C57BL/10 background showed a mild degree of gray matter inflammation but no demyelination. In conclusion, NK cells are critical effectors in protecting against TMEV-induced gray matter disease, whereas a different population of either NK1.1- NK cells, or other activated lymphocytes may be critical in resistance/susceptibility to demyelination.     

Plasmodium yoelii: antibody response in resistant and susceptible mouse strains

The numbers of antigen-reactive antibody-secreting cells, levels of parasite antigen-specific serum antibodies and numbers of red blood cells staining positive for surface immunoglobulin were determined for susceptible and resistant mouse strains following infection with Plasmodium yoelii 17x. As a control, these parameters also were measured using antigen prepared from normal red blood cells. The relatively susceptible C57BL/6 mice produced more antigen-specific antibody-secreting cells and had higher levels of immunoglobulin positive red blood cells than did DBA/2 mice, but the DBA/2 mice had more antigen-specific IgG in their sera. Both mouse strains possessed cells secreting antibody reactive with soluble normal red blood cell antigen; however, C57BL/6 mice had more IgG positive unparasitized RBC than did DBA/2 mice. Despite possessing fewer antibody positive normal RBC, DBA/2 mice had significantly higher levels of serum antibodies that reacted with soluble red blood cell antigen. These data indicate that levels of serum antibody may not reflect the amounts of antibody produced and that use of any single assay to assess the magnitude of the antibody response may give rise to misleading results.     

IL-4 is required to prevent filarial nematode development in resistant but not susceptible strains of mice

The murine Litomosoides sigmodontis model of filarial infection provides the opportunity to elucidate the immunological mechanisms that determine whether these nematode parasites can establish a successful infection or are rejected by the mammalian host. BALB/c mice are fully susceptible to L. sigmodontis infection and can develop patent infection, with the microfilarial stage circulating in the bloodstream. In contrast, mice on the C57BL background are largely resistant to the infection and never produce a patent infection. In this study, we used IL-4 deficient mice on the C57BL/6 background to address the role of IL-4 in the development of L. sigmodontis parasites in a resistant host. Two months after infection, adult worm recovery and the percentage of microfilaraemic mice in infected IL-4 deficient mice were comparable with those of the susceptible BALB/c mice while, as expected, healthy adults were not recovered from wild type C57BL/6 mice. The cytokine and antibody responses reveal that despite similar parasitology the two susceptible strains (BALB/c and IL-4 deficient C57BL/6) have markedly different immune responses: wild type BALB/c mice exhibit a strong Th2 immune response and the IL-4 deficient C57BL/6 mice exhibit a Th1 response. We also excluded a role for antibodies in resistance through infection of B-cell deficient C57BL/6 mice. Our data suggest that the mechanisms that determine parasite clearance in a resistant/non-permissive host are Th2 dependent but that in a susceptible/permissive host, the parasite can develop in the face of a Th2 dominated response.     

Resistance of C57BL/6 mice to amoebiasis is mediated by nonhemopoietic cells but requires hemopoietic IL-10 production

Resistance to intestinal amoebiasis is mouse strain dependent. C57BL/6 (B6) mice clear Entamoeba histolytica within hours of challenge, whereas C3H and CBA strains are susceptible to infection and disease. In this study, we show using bone marrow (BM) chimeric mice that mouse strain-dependent resistance is mediated by nonhemopoietic cells; specifically, B6 BM --> CBA recipients remained susceptible as measured by amoeba score and culture, whereas CBA BM --> B6 recipients remained resistant. Interestingly, hemopoietic IL-10 was required for maintaining the resistance of B6 mice, in that B6 IL-10-deficient mice and IL-10(-/-) BM --> wild-type recipients, but not IL-10(+/+) BM --> IL-10(-/-) recipients, exhibited higher amoeba scores than their wild-type controls. Additionally, C57BL/10 IL-10(-/-)Rag2(-/-) mice exhibited diminished amoeba scores and culture rates vs IL-10(-/-) mice, indicating that lymphocytes potentiated the susceptibility of IL-10-deficient mice. We conclude that nonhemopoietic cells mediate the natural resistance to intestinal amoebiasis of B6 mice, yet this resistance depends on hemopoietic IL-10 activity.     

Plasmodium chabaudi AS: erythropoietic responses during infection in resistant and susceptible mice.

The course of anemia and the erythropoietic response in the bone marrow, spleen, and blood were studied during Plasmodium chabaudi AS infection in resistant C57BL/6 (B6) and susceptible A/J (A) mice. Infections in B6 mice were characterized by moderate levels of both parasitemia and anemia and survival. In contrast, A mice experienced high parasitemia, severe anemia, and high mortality rates. During the period of anemia, erythropoiesis, as measured by in vivo 59Fe incorporation, was significantly more depressed in bone marrow and more increased in the spleen in resistant B6 mice. The increase in splenic 59Fe incorporation was a function of the size of the spleen. Bone marrow CFU-E were decreased to 50% of control in both strains, while splenic CFU-E were increased twofold greater in B6 mice compared to those in A mice. However, the absolute numbers of CFU-E per spleen in the two strains were not significantly different during peak parasitemia. Bone marrow BFU-E were transiently increased before peak parasitemia whereas splenic BFU-E peaked during peak parasitemia. A mice had significantly lower numbers of BFU-E per spleen on all days except at peak parasitemia. The frequency of blood-borne BFU-E and plasma erythropoietin titers was increased earlier and to a greater extent in A mice. These results suggest that an impaired amplification of late-stage splenic erythropoiesis may be an important determinant in the severity of anemia and lethality of infection with P. chabaudi AS in A mice. Moreover, these results demonstrate that the defective amplification of splenic erythropoiesis in A mice is neither caused by a defect in the mobilization of BFU-E from the bone marrow to the spleen nor caused by a defect in erythropoietin production.     

Genetic variation in testicular development in mice of the C57BL/10ScSn, C57BL/6By and BALB/cBy strains and the CXB recombinant-inbred lines

When compared with C57BL/6By mice, BALB/cBy mice had testes that were 41% heavier at 60 days of age and seminiferous tubules that were 41% greater in cross-sectional area at 120 days. Absolute testicular weight did not increase between 60 and 120 days of age in either C57BL/6By or C57BL/10ScSn mice but did in BALB mice, paralleling changes in the size of the seminiferous tubules. Significant testicular growth took place over this age period in mice of all seven of the CXB recombinant-inbred (RI) strains of mice derived from a cross of the BALB/cBy and C57BL/6By strains. The wide range of phenotypes shown by adult recombinant mice, which ranged from those with significantly heavier testes than BALB to those with testes the same size (at 60 days) as those of C57BL/10ScSn mice, implied the existence of several separable factors affecting testicular size in adults. At 30 days of age the RI lines fell into two groups; one with small testes like C57BL/6By and the other with larger testes like BALB/cBy mice. The segregation pattern for prepubertal testicular weight was identical to that for the H-2 histocompatibility locus.     

Induction of multiple chemokine and colony-stimulating factor genes in experimental Burkholderia pseudomallei infection

Melioidosis is a disease of the tropics caused by the facultative intracellular bacterium Burkholderia pseudomallei. In human infection, increased levels of IFN-gamma in addition to the chemokines interferon-gamma-inducible protein 10 (IP-10) and monocyte interferon-gamma-inducible protein (Mig) have been demonstrated. However, the role of these and other chemokines in the pathogenesis of melioidosis remains unknown. Using BALB/c and C57BL/6 mice as models of the acute and chronic forms of human melioidosis, the induction of mRNA was assessed for various chemokines and CSF (G-CSF, M-CSF, GM-CSF, IP-10, Mig, RANTES, MCP-1, KC and MIP-2) in spleen and liver following B. pseudomallei infection. Patterns of chemokine and CSF induction were similar in liver and spleen; however, responses were typically greater in spleen, which reflected higher tissue bacterial loads. In BALB/c mice, high-level expression of mRNA for all chemokines and CSF investigated was demonstrated at day 3 postinfection, correlating with peak bacterial load and extensive infiltration of leucocytes. In contrast, increased mRNA expression and bacterial numbers in C57BL/6 mice were greatest between 4 and 14 days following infection. This paralleled increases in the size and number of abscesses in liver and spleen of C57BL/6 mice at days 3 and 14 postinfection. Earlier induction of cytokine-induced neutrophil chemoattractant (KC), macrophage inflammatory protein-2 (MIP-2), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage CSF (GM-CSF) and macrophage CSF (M-CSF) mRNA was demonstrated in spleen, while MIP-2, MCP-1, IP-10 and Mig were demonstrated in liver of BALB/c mice when compared to spleen and liver of C57BL/6. The magnitude of cellular responses observed in the tissue correlated with increased levels of the chemokines and CSF investigated, as well as bacterial load. Compared with C57BL/6 mice, greater infiltration of neutrophils was observed in liver and spleen of BALB/c mice at day 3. In contrast, early lesions in C57BL/6 mice predominantly comprised macrophages. These results suggest that the inability of BALB/c mice to contain the infection at sites of inflammation may underlie the susceptible phenotype of this mouse strain towards B. pseudomallei infection.     

Multiple splenic lymphoid cell subpopulations regulate H-2 antigen expression on teratocarcinoma cells in vivo

Undifferentiated murine 402AX teratocarcinoma cells do not express MHC antigens when passaged in vitro or in vivo in genetically susceptible host mice. When passaged in vivo in genetically resistant mice, however, the tumor cells become H-2b antigen positive regardless of the H-2 haplotype of the resistant host mouse. The present studies use monoclonal anti-H-2b antibodies to corroborate these earlier findings, which were performed with conventional antisera. Previous studies have established that host bone marrow plus lymphoid cells from resistant primed donors regulate tumor cell H-2b antigen expression. Using bone marrow and mature lymphoid cell reconstitution techniques, the present studies indicate that splenic Ig- cells from genetically resistant host mice are the most efficient lymphoid cell subpopulation in tumor cell H-2b antigen induction. Ig+ spleen cells also reconstitute the capacity to induce teratocarcinoma cell H-2 antigens but are less effective than Ig- spleen cells. Tumor cell H-2 antigen induction in C57BL/6 beige mice is impaired compared to C57BL/6 hosts, which suggests that host NK cells may also be involved in tumor cell H-2 antigen induction. Reconstitution of lethally irradiated resistant hosts for teratocarcinoma cell H-2 antigen expression requires bone marrow plus resistant primed lymphoid cell subpopulations; bone marrow alone is insufficient. These results indicate that multiple splenic lymphoid cell subpopulations requiring a radiosensitive host environment and/or factor for differentiation regulate teratocarcinoma 402AX H-2b antigen expression in vivo in genetically resistant mice.     

The C5-sufficient A/J congenic mouse strain. Inflammatory response and resistance to Listeria monocytogenes

A/J mouse strain poorly responds to an inflammatory stimulus and is highly susceptible to Listeria monocytogenes (Lm) infection. This defect in the phagocyte inflammatory response caused by the C5 component of C deficiency was shown, by linkage analysis, to be the major reason for the extreme susceptibility of A/J mice to Lm infection. The importance of this genetic defect in C5 in relation to the poor macrophage inflammatory response and to the susceptibility to Lm infection was evaluated by developing a C5-sufficient congenic A/J mouse strain. This A/J.C5 mouse strain was studied for its inflammatory response and for its susceptibility to Lm infection. C5-sufficient congenic A/J.C5 mice showed a slight improvement (2X) in their level of macrophage inflammatory response; however, they did not mount an as strong response as the Listeria-resistant C57BL/6J mice which donated the C5 allele. When infected with Lm, A/J.C5 mice were found to be as resistant as C57BL/6J mice. These results suggest that the presence of C5 on an A/J background partially improves the deficient macrophage inflammatory response of that strain. This increase is sufficient to render the A/J.C5 mouse strain highly resistant to Listeria infection. A/J.C5 mouse strain represents a new tool for the study of the importance of C5 in resistance to infection and in the regulation of the macrophage inflammatory response.     

Comparative studies on the characteristics of proliferation and differentiation of spleen colony-forming cells

Using a single spleen colony transplantation technique and sex chromosome typing as a natural cytogenetic marker, most spleen colony-forming cells (CFC) in adult bone marrow or fetal livers of inbred LACA or C57 mice re-established hemopoiesis in lethally irradiated mice when the spleen colonies were sampled at 13 days after transplantation. However, most of the spleen colony-forming cells in the peripheral blood of normal mice possess little potential for proliferation and are less efficient in the re-establishment of hemopoiesis in lethally irradiated mice. The CFC population is heterogeneous in the mice. From the subsequent retransplantation of colonies from colony-forming cells in the peripheral blood, the simple assessment of spleen colony-forming units (CFU-s) content, based on the number of splenic colonies, does not reliably represent the content of hemopoietic stem cells.