Interferon gamma eliminates responding CD4 T cells during mycobacterial infection by inducing apoptosis of activated CD4 T cells.
In Mycobacterium bovis Bacille Calmette-Guérin (BCG)-infected wild-type mice, there was a large expansion of an activated (CD44(hi)) splenic CD4 T cell population followed by a rapid contraction of this population to normal numbers. Contraction of the activated CD4 T cell population in wild-type mice was associated with increased apoptosis of activated CD4 T cells. In BCG-infected interferon (IFN)-gamma knockout (KO) mice, the activated CD4 T cell population did not undergo apoptosis. These mice accumulated large numbers of CD4(+)CD44(hi) T cells that were responsive to mycobacterial antigens. Addition of IFN-gamma to cultured splenocytes from BCG-infected IFN-gamma KO mice induced apoptosis of activated CD4 T cells. IFN-gamma-mediated apoptosis was abolished by depleting adherent cells or Mac-1(+) spleen cells or by inhibiting nitric oxide synthase. Thus, IFN-gamma is essential to a regulatory mechanism that eliminates activated CD4 T cells and maintains CD4 T cell homeostasis during an immune response.
Dalton
D K
DK
Trudeau Institute, Saranac Lake, New York 12983, USA. ddalton@trudeauinstitute.org
Haynes
L
L
Chu
C Q
CQ
Swain
S L
SL
Wittmer
S
S
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002448:Cell Adhesion; D002478:Cells, Cultured; D018189:Immunomagnetic Separation; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D016177:Macrophage-1 Antigen / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013154:Spleen / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
D016177:Macrophage-1 Antigen; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase