Genetic differences in lymphoid tissue reactivity during liver regeneration in mice of different lines]

The transfer of lymphocytes together with sheep erythrocytes from partially hepatectomized mice to syngenous lethally irradiated mice (CAB and C57BL) increased the number of antibody forming cells in the recipient's spleen. The lymphocytes of CBA mice acquired this ability much earlier after the operation (in 4 hours) than those of the C57BL mice (in 17 hours). After the transfer of lymphocytes in the semisyngenous system there was a decrease of antibody forming cells during subsequent recipient's immunization with sheep erythrocytes; this was the result of the graft versus host reaction. The latter reaction was less marked in the operated than in control mice. These changes also occurred earlier after the operation in the CBA than in C57BL mice.     

Interrelations of cellular and humoral immune response and different doses of sheep erythrocytes in mice]

In experiments on CBA and C57BL/6 mice the generation of antibody-forming cells respectively either in the popliteal lymph nodes or spleen as well as a rate of delayed type hypersensitivity response (DTHR) on the background of subcutaneous (into foot) or intraperitoneal injection of different doses of sheep erythrocytes (from 10(4) to 10(8)) have been studied. In so doing two types of immune response can be isolated on the dependence upon the sensitivity threshold to antigen of DTHR and humoral immunity. Thus in C57BL/6 mice the antigen threshold for DTHR is of one time (in intraperitoneal immunization) or of a two times (in subcutaneous) lower order than for antibody response. In CBA line mice under subcutaneous immunization there can be seen quite an opposite picture while intraperitoneal immunization causes exact correlation of antigen threshold for cellular and humoral immune response.     

Interaction and migration of T- and B-lymphocytes in immune responses during carcinogenesis induced by methylcholanthrene]

The (CBA X C57BL) F1 mice were injected intramuscularly with methylcholantrene (MCA) in a dose of 0.3 mg, and their T- and B-cells ability to cooperate in the immune response against sheep red blood cells, and also migration of these cells from the thymus and the bone marrow to the spleen were studied. The MCA immunosuppressive action proved to be associated with the inhibition of migration and cooperation of T- and B-lymphocytes in the immune response. A conclusion was drawn that the immunosuppressive effect developing during the carcinogenesis was complex and it was realized at various stages of immunogenesis.     

Influence of the maternal effect on allogenic inhibition of hematopoietic stem cells]

Bone marrow cells (0,5-10(6)) of female mice of CBA or C57BL strains were injected intravenously to lethally irradiated CBA, C57BL/6, (femaleCBA X maleC57BL/6)F1 and (femaleC57BL/6 X maleCBA)F1 mice. Spleen of recipients as assayed for colony count on the 9th day after bone marrow transplantation by the method of Till and McCullouch. Stem cells of CBA mice demonstrated failure of allogenic inhibition in (CBA X C57BL/6)F1 hybrid mice and formed the same number of colonies as in the spleen of syngenic recipients. The level of allogenic inhibition of CBA stem cells transplanted to (C57BL/6 X X CBA)F1 hybrid mice was 50%. Bone marrow cells of C57BL/6 mice formed colonies in spleen of (CBA X C57BL/6)F1 mice at least in 20 times less than in syngenic combination. In the transplantation of bone marrow from C57BL/6 mice to (C57BL/6 X CBA)F1 hybrid mice the allogenic inhibition was less pronounced (77-85%) as compared with the transfer of cells to (CBA X C57BL/6)F1 hybrid mice (95%). The sex of a recipient did not influence the number of formed colonies. The different level of allogenic inhibition of parental stem cells can not be explained by the effect of linkage with sex as the female of reciprocal hybrid mice have identical structure of sex chromosomes (X(CBA)XC57BL/6). The data obtained indicate that the maternal effect affects allogenic inhibition of stem cells in parent--F1 system. It is possible that the maternal influence may be determined by cytoplasmic factors of inheritance which affect the expressivity of recessive genes Hh, controlling the inheritance of specific haematopoietic cell antigens.     

Functional activity of cells suppressing the humoral immune response in internal irradiation

In the adoptive transfer system of (CBA X C57BL/6)F1 mice, the estimation was made of the function of splenic cells, suppressors of the humoral immune response to sheep erythrocytes 1 and 6 months following the injection of 125I and 131I. Low absorbed doses of the radioactive isotopes were shown to stimulate the activity of the suppressors generated in mouse spleen.     

Relationship between T- and B-lymphocyte cooperation and their syngeneity]

Cooperation efficiency of (CBA x C57BL/6) F1 thymocytes and CBA bone marrow cells in immune response to SRBC was compared with the syngenic combination of the same cells. Selectivity of interaction of the T- and B-lymphocytes of different origin was studied in incomplete cyclophosphamines (CBA x C57BL/6) leads to CBA chimerae, where donors were primed with SRBC and the recipients were either intact or tolerant to the given antigen. F1 T-cells proved to interact with the CAB-B-cells 10-15 times less effectively than with the syngenic B-cells. It is suggested that similarity between the antigenic structure of the cell membrane of the T- and B-lymphocytes, aiding their physical contact, increased the action efficiency of the T-mediator on the B-cell.     

Drug-induced immune tolerance to sheep erythrocytes in mice of different lines]

Immunological tolerance to sheep erythrocytes was induced in mice of the CBA, C57BL/6, CC57BR, C3H, DBA/2 lines by means of combined administration of a high dose of the antigen and cyclophosphamide. The count of 19S antibody-forming cells was determined in the mouse spleen after the test injection of erythrocytes, by local hemolysis in gel. The extent of the tolerance induced proved to depend on the genotype of the animals; mice of the DBA/2 line were found to be most "sensitive" to its induction. There was revealed no correlation between the level of the immunological reactivity to sheep erythrocytes in the intact mice of different lines and the extent of its suppression in tolerance induction     

Ca++-dependent immunosuppressive effect of ethylenediaminetetraacetic acid (EDTA)]

Subcutaneous injection of a sum total dose of 6.44.10(-5) M of ethylenediaminetetraacetic acid (EDTA), which binds divalent cations, inhibits the process of accumulation of antibody-forming cells in the spleen of mice (CBA X C57BL) F1 hybrids, immunizated with sheep red blood cells. In a dose of 5.2.10(-5) M CaCl2 eliminated the immunodepressive effect of EDTA almost completely. It was assumed that EDTA action was produced through the Ca++-controlled regulation mechanism of one of the following processes: the interaction between T- and B-lymphocytes; proliferation and differentiation of T- and B-cells in the course of the immune response to sheep red blood cells. A more complex mechanism of EDTA action on the above-mentioned processes is not excluded, however.     

Immunological,Cytogenetical, and Behavioral Changes in CBA and C57BL/6 Male Mice after Pheromonal Action

Immunological and cytogenetical changes were studied in mice-recipients of CBA and C57BL/6 lines as well as modifications of their behavior appearing as a result of action of various stressors. Post-stress volatile excretions of CBA males cause led to a pronounced immunosuppression in males-recipients of both lines. This resulted in a decrease of capability for immune response of the stressed mice to sheep erythrocytes. Besides, in young males of the CBA line, frequency of chromosome aberrations in bone marrow cells increased statistically significantly after stressing by syngenec volatile excretions of mature animals. Attractive properties of volatile excretions of the CBA and C57BL/6 line males were studied. In norm, animals of both lines prefer syngenic odors of intact males donors. However, for the CBA line males, post-stress excretions from males-donors of both lines became more attractive than excretions from intact animals. Also revealed were interline differences in incidence of choice of syngenic and allogenic post-stress excretions. This can be explained both by different stress-reactivity of animals-donors and differences of recipients of the studied genotypes in selectivity to olfactory stimuli. An importance of olfactory stresses and of the revealed interline differences for explanation of some micro-and macroevolutionary synecological processes in the domestic mouse is discussed.     

Trypanosoma cruzi: Effect on B-cell-responsive and -responding clones

During the course of Trypanosoma cruzi infection in C57BL/6 mice, which are relatively resistant to the parasite, the hosts developed antibody activity against previously unencountered antigens. The anti-sheep erythrocyte and antitrinitrophenyl antibody levels increased rapidly from Day 7 of infection, reached a peak by the 21st day, and were maintained at this level through 120 days postinfection in these mice. In contrast, highly susceptible C3H(He) mice did not have demonstrable antibody responses to SRBC or TNP during the 24-day infection period. Autoantibody activity against the selfantigens presented on isologous erythrocytes or thymocytes, however, were reduced in infected C57BL/6 mice. No significant reduction in autoreactivity to the self-antigens on erythrocytes or thymocytes was observed in C3H(He) mice infected with T. cruzi although a trend of reduced autoresponsiveness toward erythrocytes appeared to be developing by the time of death. C57BL/6 mice immunized with sheep erythrocytes as neonates and infected with T. cruzi as adults, or adult mice primed with low doses of sheep erythrocytes prior to infection, had elevated antibody responses to sheep erythrocytes unless the mice were immunized with sheep erythrocytes during the course of infection, in which case suppression of the response against sheep erythrocytes resulted. The nonspecific synthesis of immunoglobulins in infected C57BL/6 mice was, in part, a result of the lymphocyteactivating properties of T. cruzi-associated antigens. The T. cruzi-associated antigens induced proliferative and differentiative responses in spleen cells in vitro. It is proposed that the T. cruzi-associated antigens differentially affect lymphocytes capable of responding to antigen and those lymphocytes previously stimulated by antigen.     

Deterioration of cellular immunity during aging. The relationship between age-dependent impairment of delayed-type hypersensitivity reactivity, interleukin-2 production capacity, and frequency of Thy-1+,Lyt-2- cells in C57BL/Ka and CBA/Rij mice

The effect of aging on the delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) in vivo and the interleukin-2 (IL-2) production capacity in vitro by spleen cells from young (17 weeks) and old (125 weeks) CBA/Rij and C57BL/Ka mice were investigated. For both CBA/Rij and C57BL/Ka mice an age-related decline in the DTH response to SRBC and the IL-2 production capacity was observed. Both parameters are mediated by Thy-1+,Lyt-2- spleen cells. For both mouse strains the proportion of Thy-1+,Lyt-2- spleen cells declined less strongly with aging than the DTH reactivity and the IL-2 production capacity. From this it was concluded that not only a quantitative but also a qualitative decrease of T-cell function occurs during senescence. It was also investigated whether the proportion of Thy-1+,Lyt-2- peripheral blood lymphocytes can be used as a predictive value with regard to the decline of DTH with aging of the corresponding mouse. This was indeed found to be the case in CBA/Rij mice, but not in C57BL mice.     

Graft vs host reaction in reciprocal combinations of mouse strains differing by the H-2 complex of histocompatibility]

Intraperitoneal transplantation of 0.5 x 10(7), 1 x 10(7) or 2 x 10(7) spleen cells from the C57BL mice to newborn CBA recipients induced an acute form or runt disease which resulted in the death of 43%, 86% or 95% of the recipient mice, respectively, in the course of 2--3 weeks after the cell transfer. Preliminary immunization of C57BL donors with CBA isoantigens led to a marked enhancement, and immunization with foreign antigens (sheep red blood cells)--to weakening the reaction. In reverse combination of mouse strains the runt disease was 4--5 times less severe and no "preimmunization effect" occurred. In C57BL leads to CBA combination the reaction was accompanied by proliferation of pyroninophilic mononuclears and follicular destruction, while in the CBA leads to C57BL combination-by the retardation of their growth.     

Effect of pertussis vaccine on the functional activity of the peritoneal and splenic macrophages in 2 mouse strains genetically differing by the intensity of their immune response

The immunostimulating effect of corpuscular pertussis vaccine on the antigen-presenting and bactericidal functions of peritoneal and splenic macrophages in CBA and C57BL/6 mice, differing in the intensity of immune response to sheep red blood cells and Salmonella typhimurium, has been studied. The study has revealed that the injection of pertussis vaccine alters the functional activity of the cells under study, the effect depending on the immunizing dose, the strain of mice and the time elapsed from the moment of immunization. Pertussis vaccine enhances the low capacity of macrophages for antigen presentation in C57BL/6 mice with low responsiveness and alters the resistance of peritoneal and splenic macrophages to the cytopathic action of salmonellae.     

Inhibition of the graft-versus-host response by BCGcw-induced suppressor cells or prostaglandin E1

Immunization of C57BL/6 mice with BCGcw stimulated a population of "suppressor cells" which had a decreased capacity to induce the graft-versus-host response. The graft-versus-host response was quantitated using the Simonsen splenomegaly assay. F1 mice (C57BL/6 X CBA) were inoculated intraperitoneally with 1 X 10(8) parental (C57BL/6) or (CBA) spleen cells. The F1 mice were sacrificed 13 days later and the resulting splenomegaly was 3-4 times the normal amount. F1 mice which were injected with parental BCGcw-primed C57BL/6 spleen cells had a 50% inhibition of splenomegaly, whereas BCGcw-primed CBA spleen cells (a strain which does not develop suppressor cells) did not show this inhibition. In vitro results also confirmed that only C57BL/6 mice and not CBA mice developed suppressor cells after BCGcw immunization. A second study showed that X-irradiated (1000 R) BCGcw-primed "suppressor cells" could inhibit splenomegaly caused by the inoculation of normal parental C57BL/6 cells into F1 mice. The mechanism by which BCGcw-primed "suppressor cells" caused this inhibition of splenomegaly was delineated and found to be dependent upon the secretion of prostaglandin (PGE-1). Indomethacin and aspirin, potent inhibitors of prostaglandin synthesis, blocked the activity of C57BL/6 BCGcw "suppressor cells" and splenomegaly resulted. Systemic administration of the prostaglandin (15S)-15-methyl PGE-1 reduced splenomegaly approximately 50% in F1 mice which were injected with C57BL/6 or CBA cells. These results indicated that immunization with BCGcw stimulated a population of "suppressor cells" which could cause a decrease in graft-versus-host response and that the secretion of prostaglandin was responsible for this inhibition.     

Interaction of thymus lymphocytes with histoincompatible cells. IV. Mixed lymphocyte reactions of activated thymus lymphocytes

CS7BL-activated CBA T cells (T.TDL) were obtained by thoracic duct cannulation of (CBA × C57BL)F₁ mice 4 days after heavy irradiation and injection of CBA thymus cells. T.TDL behaved differently from the TDL of normal CBA mice in unidirectional mixed lymphocyte culture in a number of respects: (a) the response of T.TDL was directed specifically against C57BL antigens, whereas normal TDL responded to both C57BL and BALB/c antigens; (b) the response of T.TDL was rapid but transient compared to that of TDL; (c) whereas only approximately 3% of TDL synthesized DNA specifically in response to C57BL antigens, as many as 25% of C57BL-activated T.TDL responded to these antigens. Evidence is presented which suggests that the T.TDL have a very limited capacity to proliferate. Most of the cells which responded to antigen synthesized DNA without subsequently entering mitosis.     

BCG-induced chronic pulmonary inflammation and splenomegaly in mice: suppression of PHA-induced proliferation, delayed hypersensitivity to sheep erythrocytes, and chronic pulmonary inflammation by soluble factors from adherent spleen cells

C57BL/6 (B6), but not CBA, mice develop intense chronic granulomatous inflammation (CGI) in the lungs and spleen in response to an iv injection with killed BCG in an oil-in-saline emulsion (BCG-E). Concomitant with the development of CGI, these mice show diminished responsiveness to PHA and LPS, as well as suppression of antibody synthesis and production of delayed hypersensitivity (DH) to sheep erythrocytes (SRBC). Suppression results from the development of adherent, Thy-1^?, Ig^? spleen cells. The present study shows that cells from inflamed spleens of BCG-E-treated B6 mice elaborate factors in vitro which (a) inhibit PHA-induced proliferation of both normal syngeneic and allogencic cells, (b) suppress DH to SRBC in B6 mice, and (c) diminish the intensity of BCG-E-induced CGI in the lungs and spleens of B6 mice. These factors are produced by adherent Thy-1^? cells in BCG-injected mice but not in similarly treated CBA mice. These factors may be important in understanding the control of immunologically mediated chronic inflammation.     

Suppressors of the graft vs graft reaction in tolerance to alloantigens

Immune response and suppressor cell activity of CBA (H-2k) mice made tolerant to allogeneic C57B1/6 (H-2b) heart graft were studied in graft-versus-graft reaction (GvGR). Intact CBA spleen cells inhibited response of (CBA X C57B1/6)F1 cells to antigenic stimulus (sheep red blood cells--SRBC), when injected together into lethally irradiated (CBA X C57B1/6)F1 mice. Spleen cells of tolerant mice were unable to decrease immune response of (CBA X C57B1/6F1 lymphocytes to SRBC and suppressed specifically the inhibition induced by intact CBA spleen cells. Spleen cells from tolerant mice were also capable of suppressing GvGR induced by CBA lymphocytes immune to C57B1/6 cells. Pretreatment of tolerant spleen cells with rabbit antithymocyte globulin and complement before adoptive transfer diminished markedly the suppression. The results obtained in the study suggest that suppression of transplantation immunity in this model is mostly due to T suppressor cells.     

The effect of aging on the induction of humoral and cellular immunity and tolerance in two long-lived mouse strains.

Aging is a complex process that adversely affects most if not all components of the immune system. In this report, two long-lived mouse strains have been compared in ability to generate both antigen-specific immunity and tolerance. Although CBA/CaJ mice produced high levels of antibody following injection of aqueous preparations of aggregated human gamma-globulin (AHGG), C57BL/6 mice made only meager antibody responses to such preparations. Age dramatically affects the humoral anti-HGG response to aqueous AHGG in both strains, but the meager response of young C57BL/6 mice was at insignificant levels in aged C57BL/6 mice. Conversely, both mouse strains generated good responses following injection of HGG in complete Freund's adjuvant at both the T and B cell level as evidenced by in vitro antigen-specific T cell proliferation and anti-HGG antibody production. Aged mice of both strains showed a marked decrease in the production of serum anti-HGG antibody in comparison to young mice. Although the antigen-specific T cell proliferative response was significantly decreased in aged CBA/CaJ mice, such proliferation was not affected in aged mice of the C57BL/6 strain. Removal of CD8+ cells from lymph node T cells of either young or aged C57BL/6 mice did not increase the antigen-specific proliferative response, suggesting that loss of CD8+ suppressors during the aging process is not responsible for the high level of antigen-specific T cell proliferation in aged C57BL/6 mice. Tolerance to HGG was readily induced in both young and aged C57BL/6 and CBA/CaJ mice although aged mice demonstrate a modest resistance to tolerance induction when compared to their young counterparts. This resistance was observed in both antibody production and antigen-specific T cell proliferation.     

Immune responses of different mouse strains after challenge with equivalent lethal doses of Toxoplasma gondii

Most immunological studies that utilize different strains of inbred mice following T. gondii infection fail to compensate for differences in host susceptibility to the size of the parasite innoculum. To address this concern, susceptible C57BL/6 and resistant CBA/J mice were orally infected with either an equivalent 50% lethal dose (LD50) of brain cysts of the 76K strain of T. gondii (15 cysts in C57BL/6, 400 cysts in CBA/J) or the same dose of parasites in each mouse strain. C57BL/6 mice receiving 400 cysts (LD50 of CBA/J mice) died post infection, whereas CBA/J mice that received 15 cysts (LD50 of C57BL/6 mice) survived. Parasite loads in the brains and serum Toxoplasma-specific IgG1 titers of LD50-infected C57BL/6 mice were significantly higher than those in LD50- or 15 cysts-infected CBA/J mice, whereas splenocyte proliferation to Toxoplasma antigen and the percentage of CD8 alpha+ T cells were reduced in LD50-infected C57BL/6 mice. In contrast, serum IgG2a and IgM titers, the percentage of gamma delta T cells and IFN-gamma expression of spleen of LD50-infected CBA/J mice were higher than those of either 15 cysts-infected CBA/J mice or LD50-infected C57BL/6 mice. These observations demonstrate that the immune response between LD50-infected C57BL/6 and CBA/J mice was more prominent when compared to C57BL/6 or CBA/J mice receiving the same parasite inoculum. These observations would suggest that caution must be excersized in the planning and interpretation of data when the size of the parasite inoculum has not been adjusted for mouse strain.