Major histocompatibility complex regulation of interleukin-5 production in the mouse

Lymph node cells of CBA (H-2^k), but not of BALB/c (H-2^d) mice immunized epicutaneously with picryl chloryde secrete interleukin (IL)-5 when stimulated with the specific antigen in vitro. The low IL-5 production in BALB/c mice persists when either picryl chloride or the unrelated antigen oxazolone are used, when the amount of antigen in vitro is varied and when a secondary response is studied. The difference in IL-5 production maps to the major histocompatibility complex (MHC) in the congenic BALB/b, BALB/c and BALB/k mice. Furthermore, lymph node cells from (k × d) F₁ mice produce IL-5 when stimulated by antigen presented on H-2^k but not on H-2^d antigen-presenting cells. Finally, the low IL-5 production in vitro in BALB/c mice is correlated with low picryl-specific IgA levels in vivo, which otherwise are ten times greater in CBA and BALB/k mice. The influence of MHC on IL-5 production and IgA secretion in the mouse might be a possible basis for the association of MHC with IgA deficiency in humans.     

NON-H-2-LINKED GENETIC CONTROL OF RESISTANCE TO BALB/c FIBROSARCOMA METH-A

The genetic control of hybrid resistance to BALB/c fibrosarcoma Meth-A was investigated. A Meth-A tumour grew slower in (BALB/c X C57BL/6)F₁ and reciprocal hybrid mice than in syngeneic BALB/c mice and was also found to grow slower in females than in males. Significant F₁ resistance was demonstrated after both subcutaneous and intraperitoneal injection of tumour cells. However, (BALB/c X DBA/2)F₁ mice did not show any significant resistance to Meth-A. In H-2 linkage studies of [BALB/c X (BALB/c X C57BL/6)] backcross mice, no statistically significant differences in the resistance of H-2 heterozygotes and homozygotes to Meth-A were observed. These results indicated that F₁ hybrid resistance to Meth-A was controlled by non-H-2-linked resistance factor(s). No linkage was observed between resistance to Meth-A and coat colour c- and b-loci.     

Influence of the genetic background and parasite load of mice on the immune response developed against nymphs of Ixodes ricinus

The immune response of BALB/c (H-2d), DBA (H-2d), C57BL/6 (H-2b), C3H (H-2k), CBA (H-2k), SJL (H-2s), and FVB (H-2q) mice infested once with 15 nymphs of Ixodes ricinus is polarized toward Th2 as suggested by cytokines produced by lymph node cells stimulated with concanavalin A. The parasite load does not influence the polarization of the immune response as observed in BALB/c mice, which developed a Th2 response when infested with 5 or 45 nymphs. As assessed by attachment and weights of engorged nymphs, no resistance was acquired by BALB/c, C57BL/6, or C3H mice undergoing three successive infestations. However, these mice produced a gradual increase in IgE. Received: 8 December 1998 / Accepted: 22 December 1998     

MULTIPLE FOREIGN NON-H-2 DETERMINANTS ON THE SURFACE OF A CHEMICALLY-INDUCED MURINE SARCOMA*

By immunizing BALB/c (H-2^d mice against normal tissues from C57BL/6J (H-2^b), C3Hf (H-2^k) and DBA/2 (H-2^d), but not from AKR (H-2^k) strains, resistance was induced to the subsequent challenge of the ‘syngeneic’ methyl-cholanthrene-induced BALB/c sarcoma ST5; lymph node cells from allo-immune BALB/c mice were also able to exert a parallel cytotoxic effect against in vitro cultured ST5 cells. The involvement of foreign H-2 specificities in the observed cross-reactions was ruled out by absorptions of H-2 monospecific sera and by the interallelic combinations used, thus suggesting that non-H-2 histocompatibility antigens were responsible for the above findings. By using the indirect isotopic antiglobulin assay, BALB/c anti-C57BL/6J and anti-C3Hf polyspecific sera were found to bind specifically to cultured ST5 cells. C57BL/6J and C3Hf, but not DBA/2, lymph node cells were able to absorb the anti-ST5 activity of the anti-C57BL/6J serum. These results indicated that ST5 cells expressed on their surface at least two different sets of foreign non-H-2 antigens: one shared by C57BL/6J and C3Hf tissues, and detected by both cell-mediated and serological techniques; the other one belonging to DBA/2 tissues, and revealed mainly at the cell-mediated level.     

Original H-2d and alien H-2k-like antigens of a BALB/c fibrosarcoma as defined by in vitro and in vivo studies of cell-mediated immunity

The present study examines the immunosensitivity and the immunogenicity of both original H-2^d and alien H-2^k-like antigens of the BALB/c (H-2^d) fibrosarcoma C-1 as detected by in vitro and in vivo cell-mediated cytotoxicity (CMC) assays. It was found that ⁵¹Cr-labeled C-1 cells were lysed in vitro by C 57 BL/6 anti-H-2^d lymphocytes. The specificity of this reaction was shown by cold inhibition experiments in which the anti-H-2^d cytotoxic activity on YC8 (H-2^d) targets was inhibited by unlabeled YC8 or C-1 but not by C3UR11 (H-2^k) tumor cells. Both D^d- and K^d-encoded antigens were recognized by appropriate cytotoxic effectors. The immunogenicity of H-2^d antigens of C-1 was revealed by the ability of C 57 BL/6 anti-C-1 lymphocytes to lyse YC8 targets. The expression of H-2^k-like alien alloantigens on C-1 was indicated by the finding that anti-H-2^k cytotoxic T lymphocytes (CTL), generated by culturing BALB/c spleen cells immune to BALB.K (H-2^k), C3Hf (H-2^k) or A (H-2^a = H-2^k/d) tissues with the cells of the same strain used for immunization, lysed C-1 targets. The cytotoxicity of these anti-H-2^k CTL against C 3 UR11 (H-2^k) targets could be specifically inhibited by cold C 3 UR 11 or C-1 cells but not by two other BALB/c tumors. Using recombinant H-2-congenic mice, it was shown that both D^k and K^k antigens were recognized by CTL on C-1 cells. The immunogenicity of the H-2^k-like antigens, however, could not be detected in vitro. In fact, effector spleen cells from BALB/c mice immune to C-1 did not develop any detectable cytotoxicity against C 3 UR 11 targets as assayed either by a direct in vitro test or after in vitro restimulation with C-1 sarcoma cells. A similar experimental design was adopted in Winn assays carried out by mixing spleen cells of BALB/c immune mice with either C-1 or C3 UR 11 targets and injecting the mixtures in BALB/c or hybrid recipients. These in vivo tests revealed the presence of both H-2^d (K^d and D^d) and H-2^k-like (K^k and D^k) antigens on C-1. At variance with the in vitro CMC assays, however, the Winn assay also detected the immunogenicity of the H-2^k alien antigens, since BALB/c anti-C-1 spleen cells were able to significantly reduce the growth of C 3 UR 11 lymphoma cells in (BALB/c × C 3 Hf)F₁ hosts.     

Diseases caused by reactions of T lymphocytes to in compatible structures of the major histocompatibility complex. I. Autoimmune hemolytic anemia

The capacities of various lymphoid cells from C57BL/10 donors to induce antibodies against red blood cells (RBC) in (C57BL/10 × DBA/2)F₁ recipients were compared: cortisone-resistant thymocytes were more potent inducers than spleen cells, and bone marrow cells were ineffective. This established a need for parental T lymphocytes in the induction of Coombs-positive hemolytic anemia by the graft-versus-host reaction (GVHR). Since some of the anti-RBC antibodies carried the Ig^c allotype specific for the F₁ host, they were autoantibodies. When antibodies were eluted from the erythrocytes of F₁ mice undergoing the GVHR (GVH F₁ mice) and subsequently tested against normal RBC in the indirect Coombs' test, the Ig^c allotype was demonstrable even on those antibodies found to react with RBC of the donor strain (C57BL/10). In addition, reactions with normal intact RBC of other strains and species were noted. Anti-RBC antibodies belonged to all Ig classes and subclasses that were tested (IgG₁, IgG_2a, IgG_2b, IgA, and IgM). By means of histocompatibility typing it was shown that the overwhelming majority of lymphoid cells from GVH animals were host cells; most of these host cells were Thy-1.2-negative. In several GVH F₁ mice Coombs-positive erythrocytes were demonstrated for periods of more than 5 months; Ig^c-positive anti-RBC antibodies were detected for periods up to 3 months. When an additional injection of parental T cells was administered to GVH F₁ mice, which had become Coombs-negative in the course of the GVHR, new anti-RBC antibodies appeared. In contrast to F₁ B cells, T cells of the F₁ host were not needed for autoimmunization as shown by the induction of anti-RBC auto-antibodies in F₁ recipients that were depleted of autologous T cells prior to the administration of parental T cells. When (C57BL/10 × DBA/2)F₁ mice were back-crossed into strain C57BL/10 and the offsprings injected with C57BL/10 (H-2^bb) lymphoid cells, most of the H-2 heterozygous (H-2^bd) back-crosses developed Coombs'-positive hemolytic anemia, whereas none of the H-2 homozygous (H-2^bb) ones did. The most likely explanation of these results is that anti-RBC autoantibodies were induced by a persistent reaction of parental T helper cells to incompatible H-2 structures on normally present autoreactive F₁ B cells. The hypothesis is proposed that reactions of T lymphocytes against virally or chemically altered structures of the major histocompatibility complex may lead to autoimmunization also in nonchimeric individuals.     

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.     

The effect of light chain gene expression on the inheritance of an idiotype associated with primary anti-(4-hydroxy-3-nitrophenyl)acetyl(NP) antibodies.

Primary anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies from C57BL/6 mice were idiotypically defined by a rabbit anti-idiotypic antiserum. The idiotypic marker detected by this antiserum (the NP^b idiotype) requires for its expression a specific heavy (H) chain-lambda (Λ) light (L) chain combination as shown in chain reassociation experiments. The idiotypic binding reaction is inhibitable by hapten. BALB/c and CBA mice also produce large amounts of Λ-bearing anti-NP antibodies, but these do not express the NP^b idiotype as defined by the rabbit antiserum. Since the NP^b idiotype could be reconstituted by reassociating C57 BL/6 anti-NP antibody H chains with either HOPC 1, or BALB/c or CBA anti-NP antibody Λ chains, the absence of the NP^b idiotype in BALB/c and CBA antibodies implies that these animals express different sets of H chain variable (V) regions in the anti-NP response. SJL mice, in contrast to other mouse strains with the Ig-1^b allotype, express only traces of NP^b idiotype in their anti-NP antibodies, the L chains of which are almost exclusively of the χ type. Knowing that SJL mice possess a regulatory gene responsible for the low level of Λ (Λ¹⁰) chains in their immunoglobulins, we have analyzed the progeny of (SJL × BALB/C)F₁, (SJL × BALB/C)F₁ × BALB/C and (SJL × BALB/C)F₁ × SJL for the expression of Λ-bearing anti-NP antibodies and NP^b idiotype. In accord with previous work (SJL × BALB/c)F₁ mice produced substantial amounts of anti-NP antibodies with the NP^b idiotype. Backcross of these mice to BALB/c revealed linkage of the NP^b idiotype to the Ig-1^b allotype, in agreement with previous data. Backcross of the F₁ animals to SJL demonstrated control of the NP^b idiotype by the gene regulating Λ chain expression in serum immunoglobulin. Chain reassociation experiments showed that in SJL mice, the regulation against Λ chain expression prevents the selection in the anti-NP response of those H chains that together with Λ chains constitute the NP^b idiotype. Apparently, these H chains are unable to contribute to a binding site with specificity for the NP hapten when combined with χ chains.     

Protection of newborn mice from graft versus host disease by maternal pre-immunization

Alloimmunization of BALB/c (H-2d) female mice with allogeneic spleen cells from C57BL/6 (H-2b) or CBA/H (H-2k) mice protects BALB/c offspring from graft-versus-host disease (GVH-D) following neonatal intraperitoneal inoculation of high doses of spleen cells respectively of C57BL/6 or CBA/H strains of mice. The mice survived GVH-D over one year after the allogeneic inoculum 24-48 h after birth and they did not show any signs of GVH reaction nor splenomegaly. We show that this phenomenon is antibody mediated and affects the developing immune system of the foetus. Repeated immunization of virgin female BALB/c with anti-H-2b or anti-H-2k antisera (Ab1) can equally abrogate GVH-D in their newborn offspring challenged at 24-48 h after birth with allogeneic spleen cells of H-2b or H-2k phenotype. Our results demonstrate that protection from GVH-D is not specific to the immunizing strain and occurs when the neonatal mice are challenged with C57BL/6 or CBA/H spleen cells. There is thus crossreactivity of tolerance against H-2 specificities. In this study we also report on the in vitro cellular immune responses of the surviving GVH-resistant mice and demonstrate that these responses against both the challenge and third party lymphocytes are impaired.     

Polymorphism of a Qa-1-associated antigen defined by cytotoxic T cells. I. Qed-1a and Qed-1d

Tla^d mice have a distinct Qed-1 allele, Qed-1^d. Its product is detected by cytotoxic T cells raised in C57BW6 (H-2^b, Tla^b) mice against cells from a new recombinant, B6-TL.123⁺ (H-2^b, Tla^d/b). Qed-1^d is also found on cells from B10.M, A.CA and B10.STC90 mice. It cross-reacts weakly with Qed-1^b. (C57BL/6 X BALB/c) F₁ anti-B10. A (SR) effectors discriminate Qed-1^a and Qed-1^d, while C3H/HeJ anti-B10. BR effectors cross-react extensively. CB6F₁ anti-5R effector cells also discriminate between the Qed-1 antigens of B6-Tla^a (H-2^b, Tla^a) and those of B10. BR and other H-2k, Tla^a strains.     

Porphyromonas gingivalisvirulence in a murine lesion model: effects of immune alterations

This study utilized various mouse strains with documented alterations in immune system components to assess their contribution to modify the virulence ofPorphyromonas gingivalis. P. gingivalisW50 was cultivated on blood agar plates, harvested and used to challenge mice by subcutaneous injection on the dorsolateral surface of the back. Soft tissue lesion development was estimated by measuring the area of the spreading lesion formed by this microorganism over a period of 15 days. Challenge of various normal inbred and outbred mouse strains including: BALB/cN, BALB/cJ, BALB/c nu/+, ICR, B10.A(4R), B10.MBR, A/J, C57BL/6J, CBA/CaH, C.B-17/Icv Tacf DF and C3H/HeN with 2×10¹⁰bacteria showed similar lesion size among these strains (400 mm²). Genetically deficient mouse strains [C.B-17/Icr Tac (SCID); DBA/2 (C5 deficient); BALB/c nu/nu (T cell deficient); CBA/CaHN-XID/J (B cell deficient) and C3H/HeJ (LPS hyporesponsive)] demonstrated a lesion size which was similar to normal animals. C57BL/6J-BgJ (NK cell deficient) mice exhibited a significantly more severe lesion than the other strains tested. Following healing of the lesions, we initiated a secondary infection of the surviving animals to estimate the acquisition of protective immunity following recovery from the primary infection. Normal mice demonstrated a delayed onset and decrease in lesion size of 15 to 30% compared with the primary infection. In contrast, each of the immunodeficient strains appeared unable to develop immune protection to the secondary challenge. The findings suggest that protection against primary infections withP. gingivalisare mediated by innate immune mechanisms (PMN. NK cells). Additionally, it appears that T-cell-dependent humoral responses are critical to developing immunity to subsequentP. gingivalisinfection.     

Reduction of graft-versus-host disease in neonatal F1 hybrid mice.

Pre-immunization of BALB/c (H-2d) mothers with C57BL/10 (H-2b) or CBA/H (H-2k) spleen cells partially protected the F1 hybrid offspring of (BALB/c x C57BL/10) or (BALB/c x CBA/H) matings from graft-versus-host-disease (GVHD) induced by neonatal intraperitoneal inoculation with spleen cells of the paternal strain. The effects achieved were manifest as a reduction in mortality. Experiments to establish whether the phenomenon was antibody mediated were performed by passive pre-immunization of BALB/c mothers with alloantisera obtained from BALB/c previously immunized with C57BL/10 spleen cells. Alloantisera produced an equivalent reduction in GVHD mortality. Some of the F1 mice that survived challenge with paternal strain spleen cells were proven to be haemopoietic chimaeras using immunofluorescence with anti-MHC monoclonal antibodies and polymorphism of the enzyme glucose-phosphate-isomerase present in the strains used. The possible mechanisms of protection from GVHD in our mouse model are discussed.     

Differences in the modulation of reactive species,lipid bodies,cyclooxygenase-2, 5-lipoxygenase and PPAR-γ in cerebral malaria-susceptible and resistant mice

Proinflammatory responses are associated with the severity of cerebral malaria. NO, H₂O₂, eicosanoid and PPAR-γ are involved in proinflammatory responses, but regulation of these factors is unclear in malaria. This work aimed to compare the expression of eicosanoid-forming-enzymes in cerebral malaria-susceptible CBA and C57BL/6 and −resistant BALB/c mice. Mice were infected with Plasmodium berghei ANKA, and the survival rates and parasitemia curves were assessed. On the sixth day post-infection, cyclooxygenase-2 and 5-lipoxygenase in brain sections were assessed by immunohistochemistry, and, NO, H₂O₂, lipid bodies, and PPAR-γ expression were assessed in peritoneal macrophages. The C57BL/6 had more severe disease with a lower survival time, higher parasitemia and lower production of plasmodicidal NO and H₂O₂ molecules than BALB/c. Enhanced COX-2 and 5-LOX expression were observed in brain tissue cells and vessels from C57BL/6 mice, and these mice expressed higher constitutive PPAR-γ levels. There was no translocation of PPAR-γ from cytoplasm to nucleus in macrophages from these mice. CBA mice had enhanced COX-2 expression in brain tissue cells and vessels and also lacked PPAR-γ cytoplasm-to-nucleus translocation. The resistant BALB/c mice presented higher survival time, lower parasitemia and higher NO and H₂O₂ production on the sixth day post-infection. These mice did not express either COX-2 or 5-LOX in brain tissue cells and vessels. Our data showed that besides the high parasite burden and lack of microbicidal molecules, an imbalance with high COX-2 and 5-LOX eicosanoid expression and a lack of regulatory PPAR-γ cytoplasm-to-nucleus translocation in macrophages were observed in mice that develop cerebral malaria.     

Lack of F1 anti-parental resistance in H-2b/d F1 hybrids devoid of β2-microglobulin

F₁ hybrid mice often reject parental hematopoietic grafts, a phenomenon known as hybrid resistance. Hybrid resistance is mediated by natural killer (NK) cells and although the molecular interactions responsible for this phenomenon are largely unknown, one hypothesis suggests that parental cells are rejected because they fail to express a complete set of host major histocompatibility complex (MHC) class I molecules. Inherent in this theory is that NK cells in the F₁ hybrid are instructed by self MHC class I molecules to form an NK cell repertoire capable of reacting against cells lacking these self MHC class I molecules. Here, we show that C57BL/6 x DBA/2 mice (H-2^b/d) devoid of β₂-microglobulin (β₂m) are incapable of rejecting β₂m?/? parental C57BL/6 cells (H-2^b) both in vivo and in vitro. From this, we conclude that the development of an NK cell repertoire, at least in F₁ mice of the H-2^b/d haplotype, requires expression of MHC class I molecules complexed with β₂m.     

Cytotoxic effects of natural killer cells have no significant role in controlling infection with the intracellular protozoon Eimeria vermiformis.

The course of infection with Eimeria vermiformis in C57BL/6J; NK cell-defective C57BL/6J bg/bg; BALB/c; T-cell-defective BALB/c nu/nu; and T-cell-, B-cell-, and NK cell-defective BALB/c x C57BL/6 scid/scid bg/bg mice was monitored. For young C57BL/6J mice, the bg/bg mutants consistently produced fewer oocysts than the controls; there were no differences between older mice of these strains. Wild-type BALB/c mice were more resistant to infection than the nu/nu and scid/scid bg/bg mutants, but there was no difference between the mutants. Treatment of BALB/c mice with poly(I.C) had no effect on the course of infection. These findings confirm the ineffectiveness of NK cells in this system.     

Anti-Inulin [β-(2→1)-Linked Polyfructose] and Anti-Grass Levan [β-(2→6)-Linked Polyfructose] Antibody Response in Mice

Anti-inulin [β-(2 → 1) polyfructosan Brucella abortus (InuBA)] and anti-grass levan [β-(2 → 6) polyfructosan] antibody responses in BALB/c and C57BL mice and in their F₁ and backcross progeny, as well as in immunoglobulin congenic and Bailey recombinant inbred strains derived from BALB/c and C57BL mice, were examined. The anti-inulin antibodies could accommodate both β-(2 → 1)- and β-(2 → 6)-linked polyfructosans, and 97% of the anti-inulin plaque-forming cells (PFC) from BALB/c mice expressed the cross-reactive idiotypes (InuIdX) shared by the BALB/c inulin- and levan-binding myeloma proteins. Of the C57BL mice, only 25% produced high anti-inulin response, and none exhibited the InuIdX of BALB/c anti-inulin antibodies. The percentages of InuIdX⁺ anti-inulin PFC were also examined in other strains with high anti-inulin response. In C58 and AL mice, 80% of anti-inulin PFC were InuIdX⁺, whereas in A/He and RIII mice, only 40% were InuIdX⁺. All strains examined developed high anti-grass levan response, and the antibodies were specific for β-(2 → 6) structures and did not exhibit InuIdX. Comparison of the magnitude of the anti-inulin antibody titers in response to InuBA in BALB/c, C57BL, and their F₁ and backcross progeny, as well as in immunoglobulin congenic (i.e., B.C-8, BAB-14, and C.B-20) and recombinant inbred strains derived from BALB/c and C57BL mice, showed that all mice having the IgCH^a(BALB/c) allotype gave high anti-inulin response. In addition to the InuIdX structural genes, the effects of allotype-linked or unlinked “regulatory” genes were also indicated by the lower anti-inulin response in B.C-8 and BAB-14 mice compared with BALB/c mice and the higher anti-inulin response in C.B-20 mice compared with C57BL mice. A multigene interaction in controlling the production of the anti-inulin antibodies was implicated.     

POLYGENIC INFLUENCES ON THE LENGTH OF OESTROUS CYCLES IN INBRED MICE INVOLVE MHC ALLELES*

Genetic influences on female reproductive cycles were analysed in histocompatibilitycongenic strains of mice. Oestrous cycles of young, virgin mice of inbred-congenic strains, hybrid crosses (F₁, and parental-hybrid backcrosses (F₂) were monitored for 3 months. Oestrous cycles were categorized by length (inter-oestrous interval): 4,5,6, or 7–14 days. Mice with the following H-2 haplotypes had a greater proportion of 5-day oestrous cycles: H-2^b, H-2^r, H-2^h2, H-2^h4, and H-2ⁱ⁵. In contrast, the H-2^k and H-2^d haplotypes had mostly 4-day oestrous cycles. Influences of H-2 haplotype were seen on two genetic backgrounds, C57BL/10Sn and C3H. Non-H-2 alleles were also implied by different patterns of cycles between strains with the same H-2^b haplotype: C57BL/10Sn with predominantly 5-day cycles vs. C57BL/6J with a mix of 4- and 5-day cycles. The genetic basis for strain differences was investigation in F₁ hybrids and their backcrosses. F₁ hybrids of an H-2^b (C57BL/10Sn; 5-day cycles) and an H-2^k (B10.BR; 4-day cycles) strain had mostly 5-day cycles, indicating dominance of an H-2^b allele(s). However, F₁ hybrids from the reciprocal B6 × B10 cross (both H-2^b) also display a preponderance of 5-day cycles, indicating dominance of a non-H-2 autosomal allele from the C57BL/10Sn strain. Among F₂ mice, a ‘4-day’ phenotype segregated with homozygosity for the k haplotype (P < 0.05, χ²). These findings demonstrate the influence of genetic differences at the major histocompatibility complex on oestrous cycles.     

COINCIDENT EFFECT IN THE GRAFT-VERSUS-HOST REACTION OF BALB/c LYMPHOID CELLS DERIVED FROM MICE IMMUNE EITHER TO ALLOGENEIC NORMAL TISSUE OR TO SYNGENEIC CHEMICALLYINDUCED FIBROSARCOMATA

By using the graft-versus-host reaction (GVHR) based on the spleen enlargement test of Simonsen (1962), lymphocytes from BALB/c mice immune to syngeneic ST2 or ST5 sarcomata were shown to behave like BALB/c anti-DBA/2 lymphocytes in specifically increasing the GVHR in (BALB/c × DBA/2)F₁ newborns as compared with non-immune BALB/c cells. No such effect was evident when BALB/c anti-ST2 or anti-ST5 lymphoid cells were given to (BALB/c × C3Hf)F₁ and to (BALB/c × AKR)F₁ mice; anti-ST5 lymphocytes were also ineffective into (BALB/c × C57BL/6)F₁ newborns in which anti-ST2 lymphocytes were able to increase the GVHR over the background induced by non-immune BALB/c cells. A third immunogenic BALB/c fibrosarcoma C-1 was able to activate syngeneic lymphocytes which gave an augmented GVHR in (BALB/c × C3Hf)F₁ and (BALB/c × AKR)F₁ but not in the other hybrids. The efficacy of BALB/c anti-ST2 or -ST5 lymphocytes in reproducing a BALB/c anti-DBA/2 like anamnestic response in (BALB/c × DBA/2)F₁ mice support previous findings indicating that non-H-2 alien histocompatibility antigens of the DBA/2 strain, are expressed on these tumour cells. The GVHR induced by lymphoid cells immune to C-1 tumour are also in keeping with serological and transplantation studies (reported elsewhere) indicating the expression of foreign H-2^k antigens on this sarcoma.     

Cytomegalovirus-induced pneumonitis and myocarditis in newborn mice

Summary Genetically determined resistance to the lethal effects of infection with murine cytomegalovirus (MCMV) has been reported previously in adult and newborn mice. We examined the pathogenesis of MCMV infection in resistant (CBA, H-2^k) and susceptible (BALB/c, H-2^d) mice infected intraperitoneally on the day of birth. BALB/c mice developed a severe interstitial pneumonitis and myocarditis 10 days post-infection. Their pulmonary and cardiac tissues contained high MCMV titres and large numbers of MCMV-antigen positive cells. MCMV also infected the endothelial and myointimal cells of the coronary arteries in newborn BALB/c mice. Only limited infection and pathological changes were seen in CBA mice. Since the severe disease in BALB/c mice resembles the pneumonitis and less frequently reported myocarditis observed after perinatal HCMV infection, the newborn mouse model will be useful for studying the consequences and treatment of such infections, the influence of the host genotype on disease severity and the possible association between perinatal HCMV infection and atherosclerosis.     

MurineTaenia crassiceps cysticercosis: H-2 complex and sex influence on susceptibility

Several inbred strains of mice were infected by intraperitoneal injection of tenTaenia crassiceps cysticerci per mouse. Genes linked with the major histocompatibility complex (H-2) were found to influence parasite growth greatly, as demonstrated by the different parasite loads of H-2 congenic mice with BALB background: BALB/c (H-2d) mice were the most susceptible, whereas BALB/k (H-2k) and BALB/b (H-2b) animals were comparatively resistant. Non-H-2 genes had no significant effect on susceptibility in H-2d strains, as reflected by the similar parasite loads in BALB/c, DBA/2, and (BALB/cxDBA/2)F1 mice. Using the H-2b (BALB/b, C57BL/6J) and H-2k (C3H/HeJ, BALB/k, and C3HeB/FeJ) strains, we found that non-H-2 background genes caused a small but significant influence on parasite load. A recombinant mouse strain alleles (K^k, I^k, S^d, D^d) was also susceptible, indicating that S and/or D regions of the H-2d complex are probably involved in the control of resistance to murine cysticercosis. Females of all mouse strains were more susceptible than males. The same effects were observed for H-2 genes and sex, with two strains ofT. crassiceps differing in their rate of growth.