Activation-mediated CD4+ T cell unresponsiveness during acute Toxoplasma gondii infection in mice.
Infection of mice with Toxoplasma gondii has been shown to induce a transient state of immune down-regulation. Earlier reports have demonstrated the role of cytokines, in particular IL-10, in this host response. Here evidence is presented that T. gondii, a major opportunistic pathogen of the newborn and those with AIDS, is able to induce CD4(+) T cell apoptosis in the infected murine host. We have examined the changes in the CD4(+) T cell population that occur during acute infection in an experimental mouse model. Seventy-six percent of the CD4(+) T cell population increased in volume by day 7 post-infection and expressed T cell maturation markers (CD44(hi), IL-2Rhi, Mel-14(lo)). Further noted was a clonal activation of several CD4(+) T cell to mitogen or parasite antigen stimulation was observed, in particular Vbeta5 T cells. Addition of rIL-2 partially restored the CD4(+) T cell proliferative response in vitro. The T cell activation marker CTLA-4 could not be detected and the co-stimulatory molecule, CD28, was down-regulated. Electrophoretic and morphologic analysis of these cells post-culture demonstrated a DNA fragmentation pattern and cell death consistent with apoptosis. These studies demonstrate for the first time in a protozoan parasite that activation induced CD4(+) T cell unresponsiveness occurs during acute T. gondii infection in mice, and may be important in immune down-regulation and parasite persistence in the infected host.
Khan
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Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.
Matsuura
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Kasper
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D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis; D017209:Apoptosis / Q000276:immunology*; D018106:CD28 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D060908:CTLA-4 Antigen; D017635:Clonal Anergy / Q000276:immunology*; D005260:Female; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D019041:L-Selectin / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018960:Hyaluronan Receptors; D018796:Immunoconjugates; D007376:Interleukin-2; D008934:Mitogens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D019041:L-Selectin; D000069594:Abatacept