Xenogeneic antisera against T-lymphocyte receptors recognizing allogeneic transplantation antigens: Preparation and properties

Antireceptor sera ARS-1 (anti-CBA-anti-C57BL/6) and ARS-2 (anti-C57BL/6-anti-BALB/c) were prepared in a xenogeneic system by immunizing rabbits with alloimmune CBA anti-C57BL/6 and C57BL/6 anti-BALB/c lymphocytes and subsequent exhaustive absorption of rabbit immune sera with red blood cells, lymphocytes, liver cells, and serum from intact mice. In the cytotoxicity test, both ARS sera lysed only activated T lymphocytes of corresponding, but no other specificities, and did not affect intact lymphocytes. They did not inactivate in vitro the PFC-producing antibodies to SRBC or inhibit the immune response to SRBC and Viantigen of Salmonella typhi in adoptive transfer experiments. Pretreatment of intact CBA lymphocytes in vitro with ARS-1 plus complement suppressed their ability to induce lethal GvH disease in irradiated (CBA × C57BL/6)F₁, but not (CBA × BALB/c)F₁ recipients; similar pretreatment of C57BL/6 lymphocytes did not lower lethality among irradiated (CBA × C57BL/6)F₁ recipients. This method of preparing ARS may help to obtain highly specific antireceptor sera for regulation of the immune response to different antigens in outbred animals and in humans.     

DNA repair and sensitivity of mouse embryo fibroblasts to methyl methanesulphonate and N-methyl-N'-nitro-N-nitrosoguanidine

DNA repair synthesis and cytotoxicity were evaluated in early passage mouse embryo fibroblasts from five inbred strains (B10, CBA, C3H/A, DBA/2, BALB/c) and in BALB/3T3 IL-2 cells after the cultures had been treated for 3 h with methyl methanesulphonate (MMS) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In the presence of hydroxyurea, the incorporation of tritiated thymidine into the MMS- or MNNG-treated cells derived from B10, CBA, C3H/A or DBA/2 mice, was, at the concentrations used, significantly higher than into controls untreated with the mutagens. Under analogous experimental conditions there was no detectable DNA repair synthesis in two kinds of cells derived from BALB/c mice. MNNG was more cytotoxic to the cells derived from BALB/c mice than to those of the four remaining strains. The sensitivity of all kinds of early passage mouse fibroblasts to MMS was similar at each MMS concentration tested. Cloning efficiency of BALB/3T3 IL-2 cells exposed to MMS at the concentration of 10(-3) or 10(-4) M did not differ from that of untreated controls. The latter cells treated with MNNG at the concentration of 10(-4) or 2 X 10(-4) M did not develop colonies.     

Detection of nonspecific cytotoxicity in graft-versus-host reaction as a function of target cell type

The cytotoxic activity of spleen cells from mice undergoing graft-versus-host (GVH) reaction on ⁵¹Cr-labeled target cells was studied under in vitro conditions. Among normal tissues used as target cells, skin fibroblasts proved to be most sensitive to the nonspecific cytotoxic effects of spleen cells from mice undergoing GVH reaction, whereas kidney cells or macrophages were insensitive to these nonspecific cytotoxic effects. Of the two murine neoplastic target cells used, Sarcoma 1 cells were susceptible to these nonspecific cytotoxic effects whereas mastocyoma cells were resistant. However, the target cells which were insensitive to the nonspecific cytolytic effects, were lysed specifically by the spleen cells from animals specifically sensitized. Therefore, both specific and nonspecific cytotoxic effects of spleen cells from mice undergoing GVH reaction could be detected with appropriate targets. These results provide a basis for reconciliation of several apparently contradictory results, reported in the literature, concerning the specificity of the cytotoxic effects of specifically sensitized lymphocytes.     

Mycobacterium genavense infection in normal and immunodeficient mice

Mycobacterium genavense is a recently described microorganism causing disseminated infections in AIDS patients. In this study, we investigate its pathogenicity in mice and some mechanisms of the host response to this bacterium. Following an intravenous challenge of 10(6) organisms, M. genavense grew progressively in the spleens and livers of BALB/c and CBA mice over at least an 8-month period. Granulomas were present in the spleens, livers and lungs of the animals. The numbers of bacteria recovered from the spleens and livers were higher in BALB/c (Bcg(s)) than in CBA (Bcg(r)) mice from day 30. The role of the Bcg gene, in the early phase of infection, was supported by the fact that the bacterial load, on day 15, was higher in BALB/c than in the congenic C.D2 (Bcg(r)) mice. The role of T cells in the host response was suggested by the high susceptibility of nude mice to M. genavense infection. In vivo depletion experiments in CBA mice indicated that gamma interferon and both CD4(+) and CD8(+) T cells participate in the containment of the bacterial load.     

Specific partial depletion of graft-vs-host activity by incubation and centrifugation of mouse spleen cells on allogeneic spleen cell monolayers.

Spleen cells (from BALB/c mice immunized with the C57BL/6 lymphoma EL4, or from non-immune BALB/c) were incubated on monolayers of [C57BL/6 times BALB/cF1 (B6CF1) spleen cells on polylysine-coated polystyrene Petri plate, for 1/2 hr or for 1 hr at 37 degrees C followed by centrifugation of the monolayers for 5 min at 70 times G to 110 times G at 34 to 37 degrees C. Control monolayers were BALB/c spleen cells. As measured by the Simonsen spleen weight assay in neonatal mice, graft-vs-host (GVH) activity was partially depleted in cell populations nonadherent to B6CF1 monolayers. Residual GVH activity of these nonadherent cells was about half that of cells incubated on the control syngeneic monolayers (the mean of eight experiments was 49% +/- 11% S.D.). Two or three consecutive cycles of incubation and centrifugation did not significantly diminish the residual GVH activity, suggesting that spleen cells with GVH activity are heterogeneous with respect to binding to allogeneic target cells under the above conditions. Cell populations nonadherent to third-part [A times AL]F1 monolayers retained full activity, and cell populations partially depleted of GVH activity in B6CF1 neonates had full activity in third-party [BALB/c times AL]F1 neonates.     

Inhibition of antiskin allograft immunity induced by infusions with photoinactivated effector T lymphocytes (PET cells)

Induction of tolerance for skin allotransplantation requires selective suppression of the host response to foreign histocompatibility antigens. This report describes a new approach which employs pre-treatment with 8-methoxypsoralen (8-MOP) and ultraviolet A light (UVA) to render the effector cells of graft rejection immunogenic for the syngeneic recipient. Eight days after BALB/c mice received CBA/j skin grafts, their splenocytes were treated with 100 ng/ml 8-MOP and 1 J/cm2 UVA prior to reinfusion into naive BALB/c recipients. Recipient mice were tested for tolerance to alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), delayed-type hypersensitivity assays (DTH), and challenge with a fresh CBA/j graft. Splenocytes from BALB/c recipients of photoinactivated splenocytes containing the effector cells of CBA/j alloantigen rejection proliferated poorly in MLC and generated lower cytotoxic T-cell responses to CBA/j alloantigens in comparison with sensitized and naive controls and suppressed the MLC and CTL response to alloantigen from sensitized and naive BALB/c mice. In vivo, the DTH response was specifically suppressed to the relevant alloantigen in comparison with controls. BALB/c mice treated in this fashion retained a CBA/j skin graft for up to 42 days post-transplantation without visual evidence of rejection. These results showed that reinfusion of photoinactivated effector cells resulted in an immunosuppressive host response which specifically inhibited in vitro and in vivo responses that correlate with allograft rejection and permitted prolonged retention of histoincompatible skin grafts.     

Generation of low-dose paralysis in the absence of the ability to secrete antibody.

(CBA/N female x BALB/c male)F1 male mice carry an X-linked defect, originating from CBA/N mice, which renders them unable to generate an antibody response to SSS-III. Histocompatible (BALB/c female x CBA/N male) reciprocal F1 male hybrids do not carry the X-linked defect and therefore generate a readily detectable PFC response to SSS-III, which can be adoptively transferred into nonresponding reciprocal F1 male mice. In the present work, we show that this adoptive response could be inhibited in recipient (CBA/N female x BALB/c male)F1 male nonresponding mice in which low dose paralysis had been induced. Evidence is presented which indicates that such suppression is of host rather than donor cell origin. The capacity to develop low-dose paralysis, a phenomenon that is antigen specific and has been attributed to the action of suppressor T cells, indicates that nonresponding (CBA/N female x BALB/c male) F1 males (and presumably the CBA/N progenitor strain) have the ability to recognize this antigen. Furthermore, since these animals fail to make a serum antibody response to SSS-III, the signal that activates suppressor T cells cannot be circulating antibody or antigen-antibody complexes. These findings are most consistent with the view that low-dose paralysis of the response to SSS-III is not dependent on antibody-mediated feedback inhibition; rather, it is an active process mediated by suppressor T cells.     

Influence of serum donor and recipient mouse genotype on the passive transfer of protective immunity with serum against Nematospiroides dubius

Dobson C., Brindley P. J. and Sitepu P. 1982. Influence of serum donor and recipient mouse genotype on the passive transfer of protective immunity with serum against Nematospiroides dubius. International Journal for Parasitology12: 567–572. Different strains of serum donor mice showed variations in innate immunity to primary infections with Nematospiroides dubius. Different levels of anti-N, dubius antibodies were detected in sera from these mouse strains; there was no correlation between antibody titre and numbers of worms recovered. Serum from donor wild and six laboratory strains of mice protected female Quackenbush (Q) recipients against N. dubius infections; donor mouse strain influenced the degree of protection conferred and donor serum antibody titre related to the degree of stunting of worm growth in recipient mice. Five laboratory strains of mice developed different levels of protective immunity following multiple experimental infections with N. dubius. Antibody titres in these mice were strongly correlated with the percentage protection observed after 1–4 infections: Q and CBA mice produced more anti-N. dubius antibody and were better protected than DBA/2, BALB/c and C3H mice. However BALB/c, C3H and CBA mice attained similar anti-N. dubius antibody titres after a single infection with N. dubius but serum from BALB/c gave better protection when transferred to female Q recipients than that from the other two strains. This suggested qualitative differences in the protective antibodies in sera between mouse strains. Five mouse strains were passively immunized with a uniform dose of serum from female Q donors: DBA/2 female recipients showed the least, BALB/c and C3H females were intermediate, and Q and CBA female mice attained the greatest level of passive protection against N. dubius. A close positive correlation existed between the degree of actively acquired and the level of passively acquired protection between the five strains of mice.     

Trypanosoma brucei: influence of host strain and parasite antigenic type on infections in mice

Inbred mice were infected with cloned populations of Trypanosoma brucei brucei Lister S42 under carefully controlled conditions. The course of infection was found to depend both on host strain and the antigenic type of the infecting organisms. The two antigenic types used, “NIM2” and “NIM6” had differing virulence for (CBA/H × C57BL/6)F₁ mice, and when mice were infected with parasites of one clone, trypanosomes of the other type frequently appeared after the initial population had been eliminated. Different mouse strains had varying susceptibility to clone NIM6. In most cases there was an inverse relation between the survival time and the parasite load during the first peak of parasitemia. The differences in resistance to T. brucei were unrelated to H-2 haplotype: C57BL/6 and (CBA/H × C57BL/6)F₁ were most resistant, CBA/H, BALB/c and DBA/2 less so, and C3H/He most susceptible.     

Generation of cytotoxic T lymphocytes during coxsackievirus tb-3 infection. II. Characterization of effector cells and demonstration cytotoxicity against viral-infected myofibers1.

This report describes studies characterizing the virus-specific cytotoxic effector cells which are present in the spleens of mice 7 days after infection with Coxsackievirus B-3. An in vitro 51Cr assay employing eyngeneic virus-infected neonatal fibroblasts was used to measure cytotoxic activity. Treatment of immune cells with (anti-thy-1.2) and complement abolished dtheir cytotoxic activity, but no reduction occurred when B cells were removed by incubation with anti-Ig and complement or macrophages eliminated by adherence depletion. The findings therefore imply that the cytotoxic reaction was mediated by sensitized T cells and that B cells and macrophages did not play an important role. Reciprocal assays performed with BALB/c and CBA/J cells showed that Coxsackievirus-immune spleen cells lysed infected syngeneic targets but not allogeneic targets, providing further evidence that cytotoxicity was mediated by effector T cells. In addition and in vitro assay system employing neonatal myocardial cells was developed and used to demonstrate that Coxsackievirus-infected myofibers were susceptible to destruction by immune spleen cells. The evidence suggests that mice infected with Coxsackie B viruses are able to mount a cell-mediated immune response with production of cytotoxic T cells which have the capacity to damage tissues infected with these agents.     

Induction of T15-specific suppressor T cells in mice with the CBA/N defect by neonatal injection with anti-T15 idiotype antibody

Mice with the CBA/N defect (xid) are unresponsive to phosphorylcholine (PC), To determine whether idiotype-specific suppressor T cells can also be generated in these defective mice, defective (CBA/N X BALB/c)F1 male and nondefective (CBA/N X BALB/c)F1 female or (BALB/c X CBA/N)F1 male mice were neonatally injected with antibodies specific for the major idiotype of anti-PC antibody, i.e., anti-TEPC-15 idiotype (T15id) antibody. Suppressor cell activity was examined by co-culturing spleen cells from neonatally treated F1 mice with spleen cells of normal nondefective F1 mice in the presence of antigen. Spleen cells from defective (CBA/NM X BALB/c)F1 mice treated with anti-T15id antibody demonstrated a level of suppressor activity (greater than 83% suppression) comparable to that of similarly treated nondefective F1 mice. This suppression was specific for the T15id of anti-PC response, and a Lyt-1-2+-bearing T cell population appeared to be responsible for the active suppression. These suppressor T cells recognized T15 but not PC, based on a functional absorption test. These results indicate that the CBA/N defects, including the deficiency in the anti-PC response by B lymphocytes and a possible T cell defect, do not influence the generation of T15id-specific suppressor T cells by neonatal injection with anti-T15id antibody.     

TCR V beta 8+ T cells prevent development of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease

BALB/c are genetically resistant to development of toxoplasmic encephalitis (TE) when infected with Toxoplasma gondii, whereas CBA/Ca mice are susceptible. We compared TCR Vbeta chain usage in lymphocytes infiltrated into brains between these animals following infection. TCR Vbeta8(+) cells were the most frequent T cell population in brains of infected, resistant BALB/c mice, whereas TCR Vbeta6(+) T cells were more prevalent than Vbeta8(+) T cells in brains of infected, susceptible CBA/Ca mice. Adoptive transfer of Vbeta8(+) immune T cells, obtained from infected BALB/c mice, prevented development of TE and mortality in infected athymic nude mice that lack T cells. In contrast, adoptive transfer of Vbeta6(+) immune T cells did not prevent development of TE or mortality in the nude mice. The protective activity of Vbeta8(+) immune T cells was greater than that of the total Vbeta8(-) population. In addition, Vbeta8(+) immune T cells produced markedly greater amounts of IFN-gamma than did the Vbeta8(-) population after stimulation with tachyzoite lysate Ags in vitro. Thus, Vbeta8(+) T cells appear to play a crucial role in the genetic resistance of BALB/c mice against development of TE.     

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The presence of cytotoxic T-lymphocyte precursor cells (CTLp) within BALB/c nude mice was analyzed. Allogeneic T lymphocytes were injected intravenously into BALB/c nude mice. The resulting graft versus host reaction circumvented the thymus defect of the nude mice and induced the differentiation of CTLp into anti-H-2 cytotoxic T lymphocytes.     

Suppressor T cells, distinct from "veto cells," are induced by alloantigen priming and mediate transferable suppression of cytotoxic T lymphocyte responses in vivo

Primary and secondary cytotoxic T lymphocyte responses to minor alloantigens can be suppressed by priming host mice with a high dose (10(8) cells) of alloantigenic donor spleen cells (SC). Such suppression is antigen specific and transferable into secondary hosts with T cells. One interpretation of this is that antigen-specific host suppressor T cells (Ts) are activated. Alternatively, donor Lyt-2+ T cells, introduced in the priming inoculum, may inactivate host CTL precursors (CTLp) that recognize the priming (donor) alloantigens. Donor cells that act in this way are termed veto T cells. The experiments described here exclude veto T cell participation in transferable alloantigen-specific suppression, and demonstrate the operation of an alloantigen-specific host-derived T suppressor (Ts) cell. The origin of the Ts has been studied directly by using Thy-1-disparate BALB/c mice. The cell responsible for the transfer of suppression of a secondary CTL response to B10 minors was of the host Thy-1 allotype, and so originated in the host spleen and was not introduced in the priming inoculum. Secondly, antigen-specific Ts generated in CBA female mice against B10 minors could act on CTL responses to an unequivocally non-cross-reactive-third party antigen (H-Y), provided the two antigens were expressed on the same cell membrane. Such third-party suppression is incompatible with the operation of veto T cells. Depletion of Thy-1.2+ or Lyt-2+ cells from the suppression-inducing donor SC inoculum did not abrogate suppression induction in BALB/c mice; instead, suppression was enhanced. The demonstration of veto cell activity in similarly primed mice by other groups of investigators indicates that both types of suppression may operate. However, our results show that only antigen-specific Ts can mediate the transferable suppression of CTL responses to alloantigens.     

Suppressive substance produced by T cells from mice chronically infected with Trypanosoma cruzi. III. Genetic restriction and further characterization

Earlier papers in this series reported that the culture supernatant of splenic L3T4+, Lyt-2- T cells from susceptible CBA mice chronically infected with Trypanosoma cruzi contain a SS3 that can inhibit the induction of delayed-type hypersensitivity to a wide range of Ag. The SS is a glycoprotein with an apparent molecular mass of 30 to 60 kDa and is distinct from T. cruzi Ag, IL-1, IL-2, IL-3 or IFN-gamma. It also has no effect on Th cells for antibody, cytotoxic T cells or immediate-type hypersensitivity. In this paper, we report that SS can suppress the induction of proliferating T cells but not the presentation of Ag to a cloned T cell line (D10). It also has no effect on the induction of delayed-type hypersensitivity in vitro. SS is produced by a number of inbred mouse strains irrespective of their susceptibility to infection with T. cruzi (BALB/c, highly susceptible; CBA, susceptible; C57BL/10, resistant) but only CBA mice are sensitive to the suppressive action of SS. This is so whether the SS is derived from CBA, BALB/c, or C57BL/10. The sensitivity to SS is not a feature of the H-2k haplotype inasmuch as B10.BR and BALB/k mice (also H-2k) do not respond to SS. Attempts to purify SS with a range of biochemical techniques substantially enriched the specific activity but failed to produce a substance visualizable by analytical gel electrophoresis. IEF chromatography revealed SS activity spanning a pH range from 6 to less than 4. This suggests that SS is likely to be a minor heterogeneous component of the suppressive supernatant. The genetically highly restricted nature of its action is intriguing and may explain some of the contradictory reports in the literature on this subject.     

H-2-restricted GVH reaction caused by T cells from normal donors of certain strains

A comparison has been made of lethal graft-versus-host (GVH) reactions caused by T cells from radiation chimeras and from normal mice. In the recipient strains tested, T cells from both chimeric and normal A, A.SW, and CBA mice showed H-2-restricted killing, while T cells from chimeric and normal C57BL/6 failed to show any evidence for H-2-restricted GVH reactions. With other strains tested as donors, T cells from chimeras showed H-2-restricted GVH reactions, while the corresponding normal cells showed some similarities to the chimeras but not complete H-2-restriction.[/p]     

Fate of H2-activated T lymphocytes in syngeneic hosts. III. Differentiation into long-lived recirculating memory cells.

Memory to H2 determinants was studied with an adoptive transfer system using a population of H2-activated blast T cells (T.TDL) obtained from thoracic duct lymph of irradiated F₁ hybrid mice injected with parental strain T cells. CBA T.TDL activated either to DBA/2 or C57BL determinants were transferred to syngeneic “B” mice. Thoracic duct lymphocytes (TDL) were obtained from the recipients 4–6 weeks later and tested for their capacity to produce (a) a graft-versus-host (GVH) reaction, (b) a mixed lymphocyte reaction (MLR) (measured by an in vivo technique) and (c) allograft rejection (suppression of the growth of allogeneic tumour cells in vivo). Control experiments involved testing the function of TDL obtained from “B” mice preinjected with TDL or no cells.TDL from “B” mice injected with TDL (passaged TDL) gave strong MLR and GVH reactions to both DBA/2 and C57BL determinants. Passaged T.TDL activated to C57BL antigens gave intermediate MLR and GVH reactions to the specific (C57BL) determinants but only very low responses to third-party (DBA/2) determinants; reciprocal results were obtained with passaged T.TDL activated to DBA/2 determinants. TDL from “B” mice given no cells failed to respond to either set of determinants.Since the responses by the passaged T.TDL did not exceed those by passaged TDL there was no evidence that adoptive transfer of T.TDL had conferred to the recipients a state of memory to either MLR or GVH determinants. Adoptive transfer did, however, lead to qualitative changes in the properties of T.TDL since, before transfer, they were unable to evoke GVH reactions or produce an MLR of normal kinetics.Passaged T.TDL were far superior to passaged TDL at suppressing the growth of allogeneic tumour cells. The protection was specific since protection against DBA/2 tumour cells was, cell for cell, 5–10 fold more effective with passaged T.TDL activated to DBA/2 determinants than with cells activated to C57BL determinants. No protection was observed with cells treated with anti-θ serum. The protective cells appeared to be precursors of effector cells rather than effector cells per se since they failed to lyse the tumour cells in vitro. These data suggest therefore that the descendants of T.TDL which survived after transfer to “B” mice were highly enriched in long-lived recirculating T lymphocytes reactive to determinants expressed by specific tumour allografts.     

Comparative analysis of clinics,pathologies and immune responses in BALB/c and C57BL/6 mice infected with Streptobacillus moniliformis

Streptobacillus (S.) moniliformis is a rat-associated zoonotic pathogen that occasionally causes disease in other species. We investigated the working hypothesis that intranasal infection might lead to different immune responses in C57BL/6 and BALB/c mice associated with distinct pathologies. This study confirmed with 75% mortality the known high susceptibility of C57BL/6 mice to Streptobacillus moniliformis infection in comparison to BALB/c mice which did not develop signs of disease. Main pathologies in C57BL/6 mice were purulent to necrotizing lymphadenitis and pneumonia. Significant seroconversion was recorded in surviving mice of both strains. Differentiation of IgG-subclasses revealed mean ratios of IgG2b to IgG1 below 0.5 in sera of all mice prior to infection and of BALB/c mice post infection. In contrast, C57BL/6 mice had a mean IgG2b/IgG1 ratio of 2.5 post infection indicating a Th1 immune response in C57BL/6 versus a Th2 response in BALB/c mice. Evaluation of different sentinel systems revealed that cultural and serological investigations of these animals might not be sufficient to detect infection. In summary, an intranasal S. moniliformis infection model in C57BL/6 mice leading to purulent to necrotizing inflammations in the lung, the lymph nodes and other organs associated with a Th1 immune response is described.     

Graft-vs-host reaction limited to a class II MHC difference results in a selective deficiency in L3T4+ but not in Lyt-2+ T helper cell function

Hybrid mice of the (B6 X bm12)F1 combination were inoculated i.v. with parental B6 spleen cells to induce a class II graft-vs-host disease (GVH). Such mice failed to generate in vitro cytotoxic T lymphocyte (CTL) responses that were dependent upon L3T4+ T helper cell (Th) function (e.g., anti-B6-TNP) but were capable of generating in vitro CTL responses that could be mediated by Lyt-2+ Th cells (anti-allo class I). When Th function was assayed directly by interleukin 2 (IL 2) secretion, class II GVH animals were found to be deficient in L3T4+ but not Lyt-2+ IL 2-secreting Th cells. This selective deficiency in L3T4+ Th function correlates with a selective decrease in class II GVH mice of host-derived derived L3T4+ T cells. In addition, it was found that the spleens of class II GVH mice contained cells capable of selectively suppressing L3T4+ Th function. In contrast, mice in which a class I + II GVH occurred were depleted of both L3T4+ and Lyt-2+ Th function as assessed by IL 2 production. The findings that class II GVH selectively depletes L3T4+ T cells and T cell functions are discussed with respect to the immune function of distinct T cell subsets in normal and diseased states.     

Modeling of the "universal" bone marrow using monoclonal antibodies

The data on the application of monoclonal antibodies (ICO-10) and rabbit complement for working the conditions of allogeneic bone marrow transplantation are presented in the paper. The treatment with monoclonal antibodies and bone marrow complement from BALB/c mice for 2 times prevented the development of transplant versus host reaction and completely protected lethally irradiated (CBA X X C57B1/6)FI mice-recipients from death. Thymus atrophy and the absence of T-cells in the peripheral blood was observed in these mice. The erythrocytes had markers characteristic of BALB/c and (CBA X C57B1/6)FI mice. Mouse splenocytes did not respond to the cells of donors and recipients in mixed lymphocyte culture reaction.