Infection-induced apoptosis deletes bystander CD4+ T cells: a mechanism for suppression of autoimmunity during BCG infection.
Infection with Mycobacterium bovis Bacille Calmette Guérin (BCG) induces high levels of apoptosis among activated CD4+ T cells. We have investigated the specificity of this pro-apoptotic response and its influence on CD4+ T cell mediated autoimmunity. Apoptosis induced by BCG-infection is unrelated to antigenic specificity, as demonstrated by the increased apoptosis of activated TCR transgenic CD4+ T cells of unrelated specificity. Moreover, infection-induced apoptosis promoted the deletion of CD4+ T cells activated either by peptide or anti-CD3/anti-CD28 stimulation. Infection-induced apoptosis required IFN-gamma production by the infected host, and expression of the IFN-gamma receptor on donor CD4+ T cells. We used an adoptive transfer model of experimental autoimmune encephalomyelitis (EAE) to assess the influence of infection-induced apoptosis on a CD4+ T cell-mediated response. A significantly higher level of apoptosis was seen among sorted encephalitogenic CD4+ T cells transferred to BCG-infected versus uninfected hosts. BCG-infected mice displayed a milder course of clinical disease than their uninfected counterparts and a decreased recovery of donor cells from the CNS. The data suggest that mycobacterial infection attenuates the severity of EAE, at least in part, by promoting the apoptotic elimination of autoreactive CD4+ T cells.
O'Connor
Richard A
RA
Trudeau Institute Inc., 154 Algonquin Ave, Saranac Lake, NY 12983, USA.
Wittmer
Susan
S
Dalton
Dyana K
DK
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology; D017209:Apoptosis; D015551:Autoimmunity / Q000276:immunology*; D024201:Bystander Effect / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000382:microbiology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology
D000941:Antigens; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma