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PubMed1979

Studies of congenitally immunologic mutant New Zealand mice. II. Absence of T cell progenitor populations and B cell defects of congenitally athymic (nude) New Zealand Black (NZB) mice.

Congenitally athymic (nude) mice on an NZB, NZW, and BALB/c background were produced by repetitive selective backcrossing. F'12 generation nude mice of these three strains were compared to their littermate nu/+ controls with respect to survival, histology, blood counts, splenic surface markers, response to mitogens, spontaneous plaque-forming cells, and appearance of naturally occurring thymocytotoxic antibodies (NTA). Under specific pathogen-free conditions, NZB nude mice survive less than 3 weeks, dying of a runting-like disease with infection by local normally noninvasive organisms. A contributing factor to his premature death is the relative absence of T cell progenitor populations in the NZB nude vs NZW nude or BALB/c nude groups. Furthermore, NZB nude mice have a significantly earlier appearance of NTA than nu/+ littermates and likewise appear to have heightened spontaneous polyclonal B cell responses against the haptens dansyl, nitroiodophenyl, trinitrophenyl,2,4 dinitrophenyl, and sulfonate. It is suggested that NZB mice have several critical immunologic defects, including abnormalities of thymic epithelial cells, T cell differentiation pathways, and chronically polyclonal activated B cell populations. These defects interact to produce the clinical expression of autoimmunity.

Animals↗

PubMed1977

Differences in the mechanism of tolerance to dinitrophenylated bovine gamma globulin when induced in normal adult mice or in reconstituted irradiated mice: dependence of the mechanism of tolerance on the structural organization of the lymphoid system.

Tolerance can be induced in adult mice by a single intravenous injection of 0.5 mg dinitrophenylated bovine gamma globulin. The cellular mechanism of the unresponsive state is different depending upon whether the tolerance is induced in normal intact adult mice or in reconstituted, irradiated mice. The tolerant state induced in intact mice is characterized by a high avidity of the residual antibody-forming cells in partially tolerant animals and a prompt reversibility on cell transfer. The overall properties of this unresponsive state are consistent with the hypothesis that it is mediated by the production of small amounts of high affinity antibody in response to the tolerance-inducing injection of antigen. In contrast, the unresponsiveness induced in reconstituted, irradiated mice by the same procedure was characterized by a low avidity of the residual antibody-forming cells in partially tolerant animals and stability on transfer of spleen cells from unresponsive into irradiated recipients. No suppressor cell activity was detected and mixed cell transfer studies were consitent with the view that this unresponsive state represented a B-lymphocyte clonal deletion. The presence or absence of T lymphocytes in the population of cells used for reconstituting the irradiated recipients did not effect the ease of tolernace induction or the cellular mechanism of the tolerant state which was produced. If irradiated mice reconstituted with B and T lymphocytes were rested for 2 wk before tolerance induction then a reversible "high affinity"-type tolerance is obtained such as is typical of normal intact animals. Restorationof a "normal" response to the tolerance-inducing injection of antigen is dependent upon the presence of thymus cells in the population of cells used for reconstitution. It is suggested that the structural integrity of the lymphoid tissue is critical in determining whether B cell will be rendered tolerant after exposure to antigen in vivo.

Age Factors↗

PubMed1977

Immunity to sporozoite-induced malaria infeciton in mice. I. The effect of immunization of T and B cell-deficient mice.

The cellular basis of immunity to sporozoites was investigated by examing the effect of immunization of T and B cell-deficient C57BL/6N X BALB/c AnN F1 (BLCF1) mice compared to immunocompetent controls. Immunization of T cell-deficient (ATX-BM-ATS) BLCF1 mice with x-irradiated sporozoites did not result in the generation of protective immunity. The same immunization protocols protected all immunocompetent controls. In contrast, B cell-deficient (micron-suppressed) BLCF1 mice were protected by immunization in the majority of cases. The absence of detectable serum circumsporozoite precipitins or sporozoite neutralizing activity in the micron-suppressed mice that resisted a sporozoite challenge suggests a minor role for these humoral factors in protection. These data demonstrate a preeminent role for T cells in the induction of protective immunity in BLCF 1 mice against a P. berghei sporozoite infection.

Animals↗

PubMed1977

Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) II. Cellular source and effect on responder and nonresponder mice.

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder strains of mice, but does stimulate the development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT antibody responses to GAT complexed to methylated bovine serum albumin (GAT-MBSA). Furthermore, extracts prepared from lymphoid cells of GAT-primed, but not control, nonresponder mice inhibit the development of antibody responses to GAT-MBSA by normal nonresponder mice. This suppression is specific, dose-dependent, and can be readily analyzed in vitro. The suppressive factor is a T-cell product. An extract from GAT-primed DBA/1 mice inhibits the response to GAT-MBSA by spleen cells from histoincompatible strains of mice that are nonresponders to GAT, but not strains that are responders to GAT.

Animals↗

PubMed1978

Histocompatibility difference between C3HfeB/HeN and C3H/HeN mice: tumour induced in C3HfeB/HeN mice expresses C3H/HeN-associated alloantigen.

A transplacentally induced lung tumour of C3HfeB/HeN mouse origin expresses, as a tumour-associated antigen, a normal tissue component of strain A mice. The genetic locus coding for this alloantigen has been shown to be linked to the H-2 major histocompatibility complex. In the present study we demonstrate that this antigen is also expressed on normal tissues of C3H/HeN mice. Skin grafts exchanged between C3HfeB/HeN and C3H/HeN mice are reciprocally rejected at approximately 3 weeks after grafting. C3HfeB/HeN mice were derived from C3H/HeN mice in 1945. These strains have apparently deviated since then in their genetic regulation of the expression of the MHC-linked genetic locus. The finding of the C3H/HeN-associated antigen on a C3HfeB/HeN mouse-derived lung tumour indicates that this deviation is reversible.

Animals↗

PubMed1975

Specific unresponsiveness to skin allografts in mice. IV. Immunological reactivity of mice treated with liver extracts, Bordetella pertussis, and antilymphocyte serum.

The strain-specific unresponsiveness to H-2 incompatible skin allografts induced by treatment of adult mice with single inoculations of donor strain liver extract and Bordetella pertussis vaccine, as well as three doses of antilymphocyte serum, has been investigated by several in vivo and in vitro methods, with a view to elucidating it mechanism. Lymphoid cells from mice with long surviving skin grafts were found to be reactive in graft-versus-host assays (as measured by splenomegaly or popliteal lymph node enlargement), and mixed lymphocyte culture tests gave positive results. Attempts to cause lethal runting of F1 hybrid mice injected at birth with spleen cells from unresponsive mice gave variable results. However, the injection of F1 hybrid cells into the footpads of unresponsive animals failed to elicit a significant host-versus-graft response. Although lymphoid cells from unresponsive animals did not include detectable numbers of cytotoxic cells, such cells could be generated by previous in vitro mixed lymphocyte culture stimulation or, to some degree, by the injection of the animals with F1 hybrid cells. Attempts to prevent mixed lymphocyte culture stimulation or cytotoxicity with serum from unresponsive mice failed at the serum concentrations used. The data indicate that long-term unresponsiveness in this system is maintained by the production in the hosts of factors that interfere with the cell-mediated response.

Animals↗

PubMed1979

Pathogenicity of cultivated murine leprosy bacilli of Hawaiian-Ogawa strain in mice. 4) Visceral lesions in mice produced by intraperitoneal infection.

The pathogenicity of two substrains (HO-R and HO-S) of cultivated murine leprosy bacilli was examined by intraperitoneal inoculation to various strains of mice (C3H, KK, BALA/c, DDD and C57BL/6). HO-R (Rough Form) was first isolated on 1% Ogawa's egg yolk medium from the leprous lesions produced by original Hawaiian strain (H bacilli). HO-S (Smooth Form) was dissociated in vitro during the 9th to 15th subculture of HO-R on the same kind of medium. In all the mice tested, intraperitoneal inoculation with HO-R bacilli produced progressively severe visceral lesions in the manner similar to H bacilli harvested from subcutaneous leproma. The only exception was, however in DDD strain of mice H bacilli produced only slight visceral lesions even in the later stage of infection. HO-S was much lower in the pathogenicity than the above two strains of murine leprosy bacilli. Visceral lesions produced by intraperitoneal inoculation with HO-S used to be very slight in all the strains of mice except BALB/c. BALB/c strain mice were highly susceptible to intraperitoneal as well as subcutaneous infection with HO-S. From the above observations, it is concluded that the characteristic features of pathogenicity of cultivated murine leprosy bacilli, such as mouse strain differences, are all the same regardless of infection route.

Animals↗

PubMed1979

Recognition among mice. Evidence from the use of a Y-maze differentially scented by congenic mice of different major histocompatibility types.

Previous studies of mating preference signified that mice can sense one another's major histocompatibility complex (MHC) types, probably by olfaction. This conclusion has now been substantiated by the use of a Y-maze whose two arms were differentially scented with currents of air conducted through boxes occupied by B6 (H-2b) males and by B6-H-2k congenic males. Four B6 mice, two males and two females, were successfully trained, by water deprivation and reward, to enter the arm scented by B6 or B6-H-2k males. One of the males and one of the females were trained to select the B6-scented arm; the other male and female were trained to select the B6-H-2k-scented arm. Untrained mice showed no MHC discrimination in the maze. The performance of the trained mice in distinguishing between MHC congenic homozygous F2 segregants derived from a cross of B6-H-2k with B6 was as good as their performance in distinguishing the respective inbred strains, thus essentially eliminating alternative and significant additional explanations of MHC-associated sensory discrimination. The data further indicate that chemosensory discrimination of MHC types can be entirely dissociated from sex differences and from the circumstances of mating.

Animal Communication↗

PubMed1978

Studies on brain lesion by administration of monosodium L-glutamate to mice. I. Brain lesions in infant mice caused by administration of monosodium L-glutamate.

Light-microscopic examination was performed on the brain lesions induced by monosodium L-glutamate (MSG) in neonatal and infant mice of ICR strain. Lesions characterized as cytoplasmic balooning, chromatin clumping, pyknosis and karyorrhexis of neurons were recognized in the arcuate nucleus (AN), subfornical organ, preoptic area, area postrema and cerebral cortex. The most vulnerable region was the AN in which the region near the root of the median eminence was easily damaged. The changes in the AN were severest in 7-day-old mice, but only slight in 20-day-old mice. Thresholds of inducing AN lesions in 10-day-old mice after intraperitoneal injection and force-tube feeding were 0.4 and 0.7-0.8 g/kg body weight, respectively. The threshold of retinal changes was about 2.5-fold that of AN in force-tube feeding. In neonatal mice injected daily with 4 g MSG/kg body weight, the neurons of the AN disappeared almost completely by the 4th day of intraperitoneal administration.

Age Factors↗

PubMed1979

The production of contact sensitivity by the injection into the footpads of recipients of the lymph node cells from mice 1 day after painting the skin with contact sensitizing agent: requirement for matching at the major histocompatibility complex between donor and recipient mice.

Donor mice were painted on the skin of the abdomen with the contact sensitizing agent, oxazolone. One day later 2-5 x 10(6) cells from the regional lymph nodes were injected into the footpads of recipient mice. Contact sensitivity was detected 6 days later by challenging the ears of the recipients and measuring the increase of thickness at 24 h. Good contact sensitivity was obtained when CBA cells were injected into CBA mice and BALB/c cells injected into BALB/c mice; the injection of BALB/c (H-2d) cells into CBA (H-2k) mice and vice versa failed to give rise to contact sensitivity. Hybrid F1 cells gave intermediate responses. The contact sensitivity caused by the injection of small numbers of lymph node cells into the footpad is interpreted as a mode of active immunization and the present results show that this only occurs when there is genetic matching at the major histocompatibility complex between the donor and the recipient mouse.

Animals↗

PubMed1977

Studies on immune responses to parasite antigens in mice. V. Different susceptibilities of hypothymic and intact mice to Babesia rodhaini.

Hypothymic BALB/c.nu/nu mice are more resistant than intact BALB/c.nu/+ mice to Babesia rodhaini and a proportion survive a dose of infected blood which is uniformly lethal to nu/+ mice. This proportion of nu/nu survivors is not affected by administration of an anti-Babesial drug, whereas the majority of nu/ + mice develop a long-lasting resistance to infection. The data suggest that T cell dependent activities are involved both in the acceleration of parasitaemia and in the development of drug-assisted resistance.

Animals↗

PubMed1978

Syngeneic mixed lymphocyte reaction in mice: strain distribution, kinetics, participating cells, and absence in NZB mice.

Co-culture of mouse spleen nonadherent (T-enriched cells with mitomycin C-treated unfractionated syngeneic spleen cells resulted in increased DNA synthesis in the responding T cells. The kinetics of this syngeneic mixed lymphocyte reaction (SMLR) showed that peak DNA synthesis occurred on day 5 of culture compared to day 4 for conventional mixed lymphocyte reaction (MLR). Anti-T cell antiserum plus complement treatment of the responding cell population abolished the reaction, and similar treatment of the stimulator population enhanced SMLR. These studies indicate that SMLR represents the response of T cells to non-T cells. Studies on the generation of cytotoxic T lymphocytes (CTL) in parallel cultures of T cells activated by syngeneic or allogeneic spleen cells showed no cytotoxicity of SMLR-activated cells for either PHA- or LPS-induced blasts but did show a good CTL response of allo-activated cells to both targets. Studies on the strain distribution of SMLR revealed that NZB mice manifested poor or no stimulation in SMLR whereas all other strains tested exhibited strong SMLR. This defect in NZB mice may be pathogenetically related to the autoimmune disease that develops in these mice.

Animals↗

PubMed1977

Chimeric drift in allophenic mice: analysis of changes in red blood cell and white blood cell populations in C57Bl/6 in equilibrium (A X SJL)F1, C57Bl/6 in equilibrium (CBA X CBA/H-T6)F1, and C57Bl/6 in equilibrium DBA/1 mice.

Forty-seven allophenic mice of three different types (C57BL/6 in equilibrium (A X SJL), C57BL/6 in equilibrium (CBA X CBA/H-T6), and C57BL/6 in equilibrium DBA/1) were analyzed for changes in their peripheral white blood cell composition and hemoglobin composition with age. It was found that 10 of the 47 mice showed significant changes termed "chimeric drift" in one or the other or both of these parameters. These 10 mice were classified as unstable chimeras, as opposed to the 37 stable chimeras, which showed no apparent chimeric drift. There was an excellent correlation of peripheral white blood cell and hemoglobin compositions of the stable chimeras. However, the unstable chimeras showed little or no correlation of these two markers. Possible mechanisms of chimeric drift are discussed.

Aging↗

PubMed1979

Immunoregulation in New Zealand mice. I. Failure of the transfer of syngeneic spleen or thymus cells to influence the natural disease in New Zealand mice.

Young, syngeneic thymocytes and spleen cells were administered to F1 hybrids of New Zealand Black by New Zealand White (NZB/W) mice beginning at 3 weeks of age and were continuted at 2-week intervals for 8 to 9 months. The development of autoimmunity as assessed by measuring the incidence and level of anti-DNA antibody, the degree of renal involvement, and the survival of recipient mice was evaluated and compared to a control group of animals. No significant differences were noted in these parameters in mice receiving cell transfers as compared to the control group. Therefore, in contrast to other reports, these results suggest that the transfer of young thymus or spleen cells into aging NZB/W mice fails to influence immunoregulation and the subsequent development of autoimmunity.

Animals↗

PubMed1979

Genetic studies in NZB mice. II. Hyperdiploidy in the spleen of NZB mice and their hybrids.

The presence of hyperdiploidy was studied in New Zealand black (NZB) mice and the progeny of NZB X DBA/2 crosses and backcrosses. Hyperdiploidy was observed in the spleens of a majority of NZB mice but not in DBA/2 mice at 1 year of age. In crosses of NZB with the DBA/2 strain, hyperploidy was observed only in backcrosses to NZB. Hyperdiploidy appeared to be determined by a recessivley inherited trait and was not related to the presence of other immunological abnormalities, including splenomegaly, hypergammaglobulinemia, and spontaneous antibodies cytotoxic for T cells and reactive with single-stranded DNA. Abnormal cells were not present in Concanavalin A-stimulated 48-h spleen cultures. There was no difference in the in vitro sister chromatid exchange rate between the autoimmune NZB strain and the non-autoimmune DBA/2 strain. Identification of NZB chromosomes by banding analysis showed that chromosomes 15 and 17 were frequently present in more than two copies in hyperdiploid spleen cells. NZB chromsomes also had reduced C-banding in an autosomal pair. These studies indicate that chromosomal abnormalities which occur in NZB mice may be useful as genetic and cytogenetic markers.

Age Factors↗

PubMed1979

Sex-related immunocompetence of BALB/c mice. I. Study of immunologic responsiveness of neonatal, weanling, and young adult mice.

The responses of lymphoid cells from the thymus, lymph nodes, and spleen of male and female BALB/c mice were evaluated to determine if sex-related variations in immune expression could be found. Immunologic assays used included blastogenic responses to mitogens, mixed lymphocyte responses, and direct and indirect measurement of plaque-forming cells against soluble and particulate antigens. The results indicated that responses of spleen cells from young adult female mice were higher than those of males in all comparative tests. Little or no differences between the sexes were observed in the mitogenesis of lymph nodes and thymuses. Newborn mice did not demonstrate the sex-associated immune differences. Among the weanling mice slight differences between male and female spleen cells responsiveness to mitogenic agents were observed.

Aging↗

PubMed1979

Immune response to syngeneic or autologous testicular cells in mice. I. Augmented delayed footpad reaction in cyclophosphamide-treated mice.

A delayed footpad reaction against syngeneic or autologous testicular cells was detected in mice of inbred C57BL/6, AKR and C3H/He strains. The reaction was only provoked to a measurable level if the immunization was preceded by treatment with cyclophosphamide (CY). Footpad reaction was strongest on day 6 after immunization and was detected in both male and female mice. It was found that the reaction was elicited not only with the immunizing antigen, but also with allogeneic or xenogeneic testicular antigen in mice immunized with syngeneic testicular cells.

Animals↗

PubMed1975

Failure to induce autoimmune phenomena in mice by administration of highly purified C-type particles from NZB mice.

Highly purified C-type particles from milk of NZB mice were ineffective in the transfer of Coombs positive hemolytic anemia and cryoglobulinemia to neonatal BALB/cHeA and NZC/B1 mice. Injection of neonatal NZB mice with these particles did not change the frequency or time of onset of these phenomena. Antinuclear antibodies were found in all injected animals in the same frequencies as in the control groups.

Anemia, Hemolytic, Autoimmune↗