Opportunistic infections and retrovirus-induced immunodeficiency: studies of acute and chronic infections with Toxoplasma gondii in mice infected with LP-BM5 murine leukemia viruses.

Mice infected with LP-BM5 murine leukemia viruses develop a syndrome, termed mouse AIDS (MAIDS), characterized by increasingly severe immunodeficiency and progressive lymphoproliferation. Virus-infected mice were examined for the ability to resist acute infection and to control chronic infection with the protozoan Toxoplasma gondii, a major opportunistic pathogen of individuals infected with human immunodeficiency virus. Mice infected with the retroviruses for 2 or 4 weeks responded normally to challenge with the parasite, but mice inoculated with the protozoan 8 or 12 weeks after viral infection died with acute disease due to T. gondii. Increased sensitivity to acute infection was associated with a reduced ability to produce gamma interferon (IFN-gamma) and with established changes in CD4+ T-cell function. Mice latently infected with T. gondii and then inoculated with the retrovirus mixture were found to reactivate the parasite infection, with 30 to 40% of dually infected animals dying between 5 and 16 weeks after viral infection. Reactivation was associated with reduced proliferation and impaired production of IFN-gamma in response to stimulation with soluble T. gondii antigens or to concanavalin A. Continuing resistance to lethal reactivation in the remaining mice was shown to require CD8+ T cells and expression of IFN-gamma. In addition, it was found that chronic infection with T. gondii altered the course of MAIDS by inhibiting the progression of splenomegaly and immunodeficiency and reducing the expression of both the helper and etiologic defective viruses. These results support previous studies which indicate that infection with T. gondii is controlled by synergistic interactions between CD4+ and CD8+ T cells, the functions of which are progressively impaired during the course of MAIDS.     

Suppression of T-helper type-1 immune response against Listeria monocytogenes by treatment of mice with goat antibodies to mouse IgD.

Injection of goat anti-mouse IgD antibodies (GAM IgD) to mice has been shown to induce polyclonal IgG1 and IgE production by B cells and interleukin-4 (IL-4) production by goat Ig-specific T cells. Surface IgD cross-linking also activates B cells to function as antigen-presenting cells (APC). Although the GAM IgD treatment is a well-established system for analysis of B-cell dependent antigen presentation, the influence of GAM IgD treatment on the immune response to irrelevant antigens is not known. To address this issue, we analysed effects of GAM IgD treatment on (1) the mitogen response of freshly isolated T cells, and (2) the listerial antigen-specific response after immunization with viable Listeria monocytogenes, which induces CD4+ interferon-gamma (IFN-gamma) producing protective T cells in normal mice. Spleen CD4+ T cells from the GAM IgD-treated mice produced higher levels of IL-4 but lower levels of IFN-gamma and IL-2 than those from the control mice when they were stimulated with concanavalin A (Con A) in vitro. When spleen T cells were stimulated with listerial antigen 10 days after a low dose (1/20 LD50) of L. monocytogenes infection, CD4+ T cells from the GAM IgD-treated mice showed increased IL-4 production and decreased IFN-gamma and IL-2 production compared with those from the control L. monocytogenes-infected mice. Furthermore, the GAM IgD treatment resulted in a reduction of the survival rate after a high dose (1/2 LD50) of L. monocytogenes infection. These results suggest that treatment of mice with GAM IgD suppresses the T-helper type-1 (Th1)-type T-cell response and induces a Th2-type response against irrelevant antigens, even when they are injected after GAM IgD treatment.     

Glycyrrhizin improves the resistance of MAIDS mice to opportunistic infection of Candida albicans through the modulation of MAIDS-associated type 2 T cell responses

Compared with normal mice, MAIDS mice (mice infected with LP-BM5 murine leukemia virus) exhibited an increase up to 100 times greater in susceptibility to infection with Candida albicans. The impaired resistance of MAIDS mice to the infection was recovered to levels observed in normal mice by the administration of glycyrrhizin (GR), an active component of licorice roots. MAIDS mice inoculated with CD4(+) T cells from GR-treated mice were also resistant to C. albicans infection. Normal mice inoculated with CD4(+) T helper type 2 cells (Th2 cells) from MAIDS mice were susceptible to C. albicans infection at the same levels shown in MAIDS mice. The susceptibility of normal mice inoculated with type 2 T cells was reversible by (i) administration of GR and (ii) inoculation of CD4(+) T cells from GR-treated mice and injection of a mixture of mAbs targeted against type 2 cytokines (IL-4 and IL-10). Type 2 cytokines were not detected in sera of MAIDS mice inoculated with CD4(+) T cells from GR-treated mice, while they were present in sera of MAIDS mice treated with saline. These results suggest that, by inducing CD4(+) T cells which suppress type 2 cytokine production by MAIDS-associated Th2 cells, GR improves the resistance of MAIDS mice to C. albicans infection.     

Analysis of cytokine production in the colon of nude mice with experimental colitis induced by adoptive transfer of immunocompetent cells from mice infected with a murine retrovirus

LP-BM5 murine leukemia virus (MuLV) is known to induce murine AIDS (MAIDS). We have shown that Sj?gren's syndrome (SjS)-like exocrinopathy can be induced in mice with MAIDS and that adoptive transfer of spleen cells from MAIDS mice can induce inflammatory bowel disease-like colitis as well as SjS-like exocrinopathy in nude mice. To assess the role of interferon (IFN)-gamma and interleukin (IL)-10 in the pathogenesis of our experimental model, we tried to identify the cells producing these cytokines and their localization in the colitis lesions in situ. Expression of mRNA for IFN-gamma and IL-10 was assessed by RT-PCR, and protein expression of these cytokines was also analyzed in frozen sections of colon by double-color-staining immunofluorescence (IF). An increase of IFN-gamma and IL-10 mRNA was detected in the colon of mice with colitis, but not in that of control mice. Double-color IF showed that Mac-1(+) cells were positive for IFN-gamma or IL-10 and that most CD4(+) T cells were positive for IL-10, although the population of IFN-gamma-positive CD4(+) T cells was low. In our experimental colitis model, Mac-1(+) macrophages that produce both IFN-gamma and IL-10 might play a crucial role in the pathogenesis of colitis in combination with CD4(+) T cells.     

Impaired IL-15 production associated with susceptibility of murine AIDS to mycobacterial infection

LP-BM5 murine leukemia virus (MuLV) injection causes murine AIDS (MAIDS), a disease characterized by many functional abnormalities of immunocompetent cells. We show that MAIDS mice are susceptible to Mycobacterium bovis Bacille Calmette-Guérin (BCG) infection as assessed by survival rate and bacterial counts. The peritoneal exudate macrophages from MAIDS mice produced a significant level of interleukin (IL)-12 soon after inoculation with BCG, whereas IL-15 and tumor necrosis factor (TNF) production were severely impaired in BCG-infected MAIDS mice. The appearance of natural killer (NK) and CD4+ T helper type 1 (Th1) cells specific for mycobacterial antigen were depressed in MAIDS mice after BCG infection. Thus, it appeared that impaired production of IL-15, besides other inflammatory cytokines, in MAIDS mice may be involved in the poor responses of the NK and Th1 cells, resulting in an increased susceptibility to BCG.     

Characterization of T-cell receptor gamma delta T cells appearing at the early phase of murine Listeria monocytogenes infection.

It has been shown that T-cell receptor (TcR) gamma delta + CD4- CD8- T cells increase in number and have an important role in early protection in murine Listeria monocytogenes infection. In this report, to characterize further the phenotype of the gamma delta T cells in listeriosis, we analysed V region gene usage and in vitro antigen recognition of the TcR gamma delta T cells in the peritoneal cavity of mice at the early phase after i.p. infection with a sublethal dose of L. monocytogenes. The gamma delta T cells predominantly expressed V delta 6 which has been reported to be expressed by TcR gamma delta-bearing foetal thymocyte hybridomas specific to mycobacterial and self heat-shock protein (hsp) 60. These early appearing CD3+ CD4- CD8- T cells in Listeria-infected mice, which were reported to be TcR gamma delta T cells, increased in proportion and in size by in vitro stimulation with recombinant hsp 60 from Mycobacterium bovis and purified protein derivative from M. tuberculosis but not by stimulation with heat-killed L. monocytogenes. A 65,000 MW molecule was detected in the lysate of viable L. monocytogenes but not in the lysate of heat-killed L. monocytogenes by a monoclonal antibody (mAb) raised against mycobacterial hsp 60. These results suggest that the V delta 6-bearing peripheral gamma delta T cells are activated by recognizing listerial hsp 60 expressed by viable L. monocytogenes. The hsp 60-reactive V delta 6-bearing T cells may have an important role in protection against L. monocytogenes and other parasites that express hsp 60 at high level.     

Memory phenotype CD8(+) T cells in IL-15 transgenic mice are involved in early protection against a primary infection with Listeria monocytogenes

We recently constructed IL-15 transgenic (Tg) mice using cDNA encoding a secretable isoform of the IL-15 precursor protein under the control of an MHC class I promoter. The IL-15 Tg mice exhibited resistance against a primary infection with Listeria monocytogenes. The numbers of memory CD8(+) T cells were markedly increased in the IL-15 Tg mice following Listeria infection accompanied by sustained IL-15 production. The increased CD44(+)CD8(+) T cells in the infected IL-15 Tg mice were not specialized to recognize Listeria-specific antigen but produced a large amount of IFN-gamma in response to bystander stimulation exogenous IL-15 in combination with IL-12. Furthermore, Listeria-specific Th1 response by CD4(+) T cells was significantly augmented in the IL-15 Tg mice compared with control mice following Listeria infection. In vivo depletion of the CD8(+) T cells by anti-CD8 monoclonal antibody and adoptive transfer of the T cells from naive IL-15 Tg mice indicated that the CD8(+) T cells functioned not only to eliminate bacteria at the early stage of infection but also to promote Th1 response to L. monocytogenes. Overexpression of IL-15 shed light on a novel role of memory CD8(+) T cells in early protection and promotion of Th1 response against a primary infection with L. monocytogenes.     

Effects of Z-100, a Mycobacterium-tuberculosis-derived arabinomannan, on the LP-BM5 murine leukemia virus infection in mice.

OBJECTIVE: To investigate the effects of Z-100, an arabinomannan extracted from Mycobacterium tuberculosis, on the LP-BM5 murine leukemia virus (LP-BM5 MuLV) infection in mice. METHODS: C57BL/6 mice infected intraperitoneally with 4.5 x 10(2) PFU/mouse of LP-BM5 MuLV (MAIDS mice) were treated intraperitoneally with a 10-mg/kg dose of Z-100 every other day beginning 1 day after the viral infection. MAIDS mice treated with Z-100 were compared with control mice (MAIDS mice treated with saline) for their survival and splenomegaly after LP-BM5 infection. Cytokine-producing profiles of splenic T cells from these two groups of mice were also compared. RESULTS: When MAIDS mice treated with Z-100 were compared with those of control mice, a decrease in splenomegaly and lymphadenopathy was observed. Splenomegaly was markedly enhanced in MAIDS mice treated intraperitoneally with IL-4 or IL-10. When MAIDS mice were treated with Z-100, their survival rates were significantly increased compared to those of controls. Splenic T cells from control mice produced type-2 cytokines (IL-4 and IL-10). However, a decreased production of type-2 cytokines by splenic T cells from MAIDS mice treated with Z-100 was demonstrated. CONCLUSION: Z-100 could decrease the severity of the LP-BM5 MuLV infection through the regulation of MAIDS-associated type-2 T-cell responses.     

A unique subset of normal murine CD4+ T cells lacking Thy-1 is expanded in a murine retrovirus-induced immunodeficiency syndrome, MAIDS

Some strains of mice inoculated with LP-BM5 murine leukemia virus (MuLV) develop a syndrome, termed mouse acquired immunodeficiency syndrome (MAIDS), characterized by progressive lymphoproliferation and profound immunodeficiency. LP-BM5 MuLV is a virus mixture that contains ecotropic (eco) and mink cell focus-induced MuLV and a defective genome that is the proximal cause of disease. Flow cytometry analyses of spleen and lymph nodes from susceptible C57BL/6 mice infected with this virus mixture revealed the presence in spleen and peripheral lymph nodes of a previously unrecognized subset of CD4+CD3+ T cells that are Thy-1-. The frequency of these cells increased with progression of disease, eventually comprising between 30% and 50% of all CD4+ cells. Infection of A/J mice, a strain which is genetically resistant to development of MAIDS, did not induce an increase of this T cell population, indicating that infection with the virus mixture was insufficient to induce its proliferation. A central role for the defective virus in this process was suggested by the finding that C57BL/6 mice infected with LP-BM5 eco alone did not have increased frequencies of Thy-1-CD4+ cells in spleen. Studies of spleen and peripheral lymph node cells from normal mice demonstrated the presence of Thy-1-CD4+ cells at frequencies of 1%-2%. Studies using two anti-T cell monoclonal antibodies, SM6C10 and SM3G11, that define four CD4+ subsets showed that Thy-1-CD4+ T cells from normal and infected mice were present only in the 6C10- subsets.     

CD95 (Fas) may control the expansion of activated T cells after elimination of bacteria in murine listeriosis.

CD95 (Fas) is known to mediate activation-induced T-cell death by apoptosis. To understand the role of CD95 during the course of bacterial infection, we examined the kinetics of alphabeta and gammadelta T cells in the peritoneal cavities and livers of 5-week-old CD95-defective MRL/lpr mice after an intraperitoneal infection with Listeria monocytogenes. The number of bacteria in the spleen decreased to an undetectable level by day 10 after infection with 7 x 10(3) Listeria cells similar to the number in MRL/+/+ mice. The number of alphabeta T cells expressing CD44 and CD95 reached a maximum in the peritoneal cavity on day 6 after listerial infection and thereafter decreased gradually in MRL/+/+ mice, whereas CD44+ alphabeta T cells without CD95 expression continued to increase throughout the course of listerial infection in MRL/lpr mice. Freshly isolated T cells from MRL/+/+ mice infected with L. monocytogenes 10 days previously showed DNA fragmentation with apoptosis, whereas such fragmentation was not prominent in T cells from infected MRL/lpr mice. In correlation with the increased number of CD44+ alphabeta T cells, Listeria-specific T-cell proliferation of peritoneal exudate cells was significantly greater in MRL/lpr mice than in MRL/+/+ mice on day 10 after listerial infection. In contrast to alphabeta T cells, gammadelta T cells increased in number only transiently in the peritoneal cavity and liver after listerial infection in both MRL/lpr mice and MRL/+/+ mice. These results suggest that CD95-mediated cell death with apoptosis may be involved in termination of the alphabeta-T-cell-mediated immune response after the battle against L. monocytogenes has been won, whereas gammadelta T cells may undergo apoptosis independently of CD95 during the course of listerial infection.     

The xid mutation plays an important role in delayed development of murine acquired immunodeficiency syndrome

Infection of C57BL/6 mice with LP-BM5 murine leukemia virus (MuLV) leads to the development of murine acquired immunodeficiency syndrome (MAIDS) characterized by abnormal lymphoproliferation, hypergammaglobulinemia and severe immunodeficiency. Progression of MAIDS is delayed in X chromosome-linked immunodeficient (XID) mice, which have an abnormality of Bruton's tyrosine kinase (Btk) and lack functionally mature B cells including CD5+ B cells. In this study, we report the following four major findings. (i) Susceptibility to disease induction is not reconstituted by transfer of CD5+ B cells to XID mice. (ii) Spleen cells from asymptomatic XID mice are able to transmit MAIDS to wild-type mice. (iii) MAIDS can be transmitted to XID mice with the transfer of B cells, but not T cells, from C57BL/6 mice with MAIDS. (iv) Cells which undergo massive lymphoproliferation in XID mice with MAIDS by cell transfer are of host origin, but are not from the donor. We suggest from these results that a B cell subpopulation that is impaired in XID mice plays an important role in the initiation of MAIDS.      

Hot water extracts of Chlorella vulgaris reduce opportunistic infection with Listeria monocytogenes in C57BL/6 mice infected with LP-BM5 murine leukemia viruses

The bacterial elimination after infection with Listeria monocytogenes was impaired in mice with murine acquired immunodeficiency syndrome (MAIDS) by infection with LP-BM5 murine leukemia virus. Oral administration of hot water extracts of Chlorella vulgaris (CVE) restored the capacity of MAIDS mice to eliminate L. monocytogenes in association with improvement of the deteriorated immune response to L. monocytogenes. DTH response to Listeria in CVE-treated MAIDS mice was significantly higher than that of MAIDS mice after Listeria infection in association with increases in number of CD4⁺CD8⁻ and CD4⁻CD8⁺ αβ T-cells in the infected sites. CVE might be effective in the treatment of opportunistic infection in retrovirus-induced immunodeficient patients.     

Analysis of the Capacity to Produce IL-3 in Murine AIDS

Adult C57BL/6 mice infected with LP-BM5 murine leukaemia virus represent a model of murine AIDS (MAIDS). In this study we have analysed the capacity of CD4⁺ T cells from infected mice to produce IL-3 following stimulation with ConA for 24–72 h. In contrast to the position with IL-2, the production of which is markedly impaired during LP-BM5 infection, similar levels of IL-3 were measured in culture supernatants of splenocytes from infected and uninfected mice harvested at 24 h of stimulation. Forty eight and 72 h of ConA stimulation led to increasing levels of IL-3 being measured in cultures from uninfected mice, whilst in cultures from infected animals, IL-3 levels remained stagnant. Similar results were obtained 4, 8 and 13 weeks post-infection. In view of the fact that parallel experiments revealed markedly impaired proliferative responses to ConA during MAIDS, we conclude that IL-3 production is basically intact at the cellular level in T cells during MAIDS; but when in a situation requiring clonal expansion of the activated T cells, IL-3 production will be inhibited owing to the impaired capacity for proliferation.     

CD4+ T cells in murine acquired immunodeficiency syndrome: evidence for an intrinsic defect in the proliferative response to soluble antigen

C57BL/6 mice inoculated with LP-BM5 murine leukemia viruses develop an immunodeficiency syndrome, termed murine acquired immunodeficiency syndrome (MAIDS), characterized by a variety of functional abnormalities of T and B cells. In the present study, we have analyzed the ability of lymph node cells from infected mice to generate secondary in vitro proliferative responses to soluble antigens. Our data demonstrate that the ability of lymph node cells to proliferate in response to soluble antigen or T cell mitogens declines progressively during the course of MAIDS. Impaired proliferative responses were shown to be characteristic of purified CD4+ but not CD8+ cells from infected mice when stimulated in the presence of normal accessory cells. In addition, the impaired responses of unseparated lymph node cells from infected mice could be reconstituted by the addition of purified CD4+ T cells from nodes of primed normal animals. These results strongly suggest that an intrinsic CD4+ T cell defect developing during the course of MAIDS contributes significantly to impaired responses to mitogens and to impaired secondary in vitro proliferative responses to soluble antigen.     

Effective induction of acquired resistance to Listeria monocytogenes by immunizing mice with in vivo-infected dendritic cells

Splenic dendritic cells (DCs) obtained from mice at 48 h after Listeria monocytogenes infection exhibited up-regulation of CD80 and produced higher titers of gamma interferon (IFN-gamma) and interleukin-12 (IL-12) than did DCs obtained from uninfected mice. Mice immunized with DCs obtained from mice that had been infected with L. monocytogenes 48 h before acquired host resistance to lethal infection with L. monocytogenes at 4 and 8 weeks. Immunization with DCs from heat-killed L. monocytogenes failed to induce resistance. Acquired antilisterial resistance is specific, since the immunized mice could not be protected from Salmonella enterica serovar Typhimurium infection. Infected DCs stimulated proliferation of naive CD4(+) and CD8(+) cells in vitro, suggesting that in vivo-infected DCs activate CD8(+) T cells, which are critical in acquired antilisterial resistance, as well as CD4(+) T cells. When wild-type mice were immunized with DCs from IFN-gamma-deficient mice, they were protected against a lethal L. monocytogenes challenge. In contrast, when mice were immunized with DCs from anti-IL-12 p40 monoclonal antibody-injected mice, they failed to gain acquired antilisterial resistance. These results suggest that DC-derived IL-12, but not IFN-gamma, may play a critical role in induction of acquired antilisterial resistance. Our present results suggest that splenic DCs obtained from mice infected with L. monocytogenes in vivo may be an effective immunogen with which to induce antigen-specific immunity.     

Protective effect of cyclosporin A on immune abnormalities observed in the murine acquired immunodeficiency syndrome.

The murine leukemia viruses (MuLV) designated LP-BM5 induce an immunodeficiency disease in susceptible strains of mice with many features in common to human acquired immunodeficiency syndrome (AIDS), including lymphadenopathy and profound immunodeficiency associated with enhanced susceptibility to infection and terminal B cell lymphomas. The disease, termed murine AIDS (MAIDS), crucially depends on the presence of B cells and CD4+ T cells, suggesting that mutual activation of these two cell types is central in the pathogenesis of the immunodeficiency syndrome. Cyclosporin A (CsA), whose immunosuppressive effect is attributed mainly to inhibition of interleukin 2 and interferon-gamma expression, interferes in T-B cell interactions. Here we show that chronic treatment with CsA (40 or 60 mg/kg/day) before and after infection with LP-BM5 MuLV protects against the development of immunodeficiency disease as assessed by functional, serological and histopathological criteria. The protection was not complete, suggesting both CsA-sensitive and CsA-resistant components to the pathogenesis of this syndrome, and was found to be independent of ecotropic MuLV expression. These results underline immunopathological mechanisms in the progression of immune abnormalities in MAIDS that are susceptible to inhibition of CsA and may serve as an experimental basis for developing a treatment of the human disorder with immunomodulators.     

Modification of thymic cell subsets induced by long-term cocaine administration during a murine retroviral infection producing AIDS.

LP-BM5 murine leukemia virus (MuLV) infection and cocaine administration are known to impair the murine immune system. We have developed a murine model to study the effect of daily cocaine administration and retrovirus infection on the lymphoid cell populations of the thymus. C57BL/6 female mice were studied following chronic cocaine administration for 11 weeks with simultaneous LP-BM5 MuLV infection. Cocaine administration reduced body and thymus weight, significantly reduced the number of CD8+ cells in the thymus, and partially prevented thymus enlargement due to lymphoid cell proliferation induced by LP-BM5 MuLV infection. Retrovirus infection was associated with a decrease in the percentage and absolute number of Thy 1.2+, CD4+, and CD8+ cells in the thymus, an effect potentiated by cocaine administration. Therefore cocaine impairs thymic function by altering the number of cells expressing T cell differentiation markers in MAIDS.     

Memory phenotype CD8+ T cells with innate function selectively develop in the absence of active Itk

T cells with a memory-like phenotype and possessing innate immune function have been previously identified as CD8(+)CD44(hi) cells. These cells rapidly secrete IFN-gamma upon stimulation with IL-12/IL-18 and are involved in innate responses to infection with Listeria monocytogenes. The signals regulating these cells are unclear. The Tec kinase Itk regulates T cell activation and we report here that a majority of the CD8(+) T cells in Itk null mice have a phenotype of CD44(hi) similar to memory-like innate T cells. These cells are observed in mice carrying an Itk mutant lacking the kinase domain, indicating that active Tec kinase signaling suppresses their presence. These cells carry preformed message for and are able to rapidly produce IFN-gamma upon stimulation in vitro with IL-12/IL-18, and endow Itk null mice the ability to effectively respond to infection with L. monocytogenes or exposure to lipopolysaccharides by secretion of IFN-gamma. Transfer of these cells rescues the ability of IFN-gamma null mice to reduce bacterial burden following L. monocytogenes infection, indicating that these cells are functional CD8(+)CD44(hi) T cells previously detected in vivo. These results indicate that active signals from Tec kinases regulate the development of memory-like CD8(+) T cells with innate function.     

Effect of a retroviral immunodeficiency syndrome on murine cytomegalovirus-induced hepatitis.

We have studied the effects of LP-BM5 MuLV-induced murine acquired immunodeficiency syndrome (MAIDS) on concomitant murine cytomegalovirus (MCMV) infection in the livers of C57BL mice. A delayed inflammatory response in livers of mice with MAIDS (M+) on day 4 was associated with impaired clearance of MCMV-infected cells 6 days after infection. This correlated with increased levels of inflammation and serum alanine transaminase. The latter reflects enhanced hepatic necrosis, which was evident histologically. Delayed-type hypersensitivity responses to MCMV antigen were unimpaired in M+ mice and were mediated by CD8+ cells. Depletion of NK1.1+ cells from M+ mice increased MCMV replication and associated liver damage on day 6, whereas CD8+ depletion had little effect. In contrast, in the presence of CD8+ cells M- C57BL mice did not require NK1.1+ cells for control of hepatic MCMV infection, but dual NK1.1+ and CD8+ depletion dramatically potentiated hepatic MCMV replication. Our results suggest that M+ mice may acquire non-NK1.1+ and non-CD8+ cells that are able to partially control hepatic MCMV infection. These findings are discussed with reference to mortality in M+ mice after high-dose MCMV infection, as this is initially delayed but ultimately higher than in M- controls.     

Unique CD4(+) T cells in TCR alpha chain-deficient class I MHC-restricted TCR transgenic mice: role in a superantigen-mediated disease process.

Mice carrying a transgenic TCR with targeted disruption of the TCR alpha chain (H-Y alpha(-/-)) possess CD4(+) T cells which express the transgenic TCR beta without the alpha chain. These mice developed the murine acquired immunodeficiency syndrome (MAIDS) after infection with LP-BM5 retroviruses, a process which requires CD4(+) T cells. These cells are negative for TCR delta chain and pre-TCR alpha chain expression, and thus express a unique surface receptor with the TCR beta chain as a component. The cells respond to MAIDS virus-associated superantigen and concanavalin A, but not to protein antigens such as ovalbumin. Thus, this novel surface receptor appears to play an important role in the pathogenesis of MAIDS.