Interferon γ eliminates responding CD4 T cells during mycobacterial infection by inducing apoptosis of activated CD4 T cells

DK Dalton, L Haynes, CQ Chu, SL Swain… - The Journal of …, 2000 - rupress.org
DK Dalton, L Haynes, CQ Chu, SL Swain, S Wittmer
The Journal of experimental medicine, 2000rupress.org
In Mycobacterium bovis Bacille Calmette-Guérin (BCG)-infected wild-type mice, there was a
large expansion of an activated (CD44hi) 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)-γ knockout (KO) mice, the activated CD4 T cell
population did not undergo apoptosis. These mice accumulated large numbers of CD4+ …
In Mycobacterium bovis Bacille Calmette-Guérin (BCG)-infected wild-type mice, there was a large expansion of an activated (CD44hi) 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)-γ knockout (KO) mice, the activated CD4 T cell population did not undergo apoptosis. These mice accumulated large numbers of CD4+CD44hi T cells that were responsive to mycobacterial antigens. Addition of IFN-γ to cultured splenocytes from BCG-infected IFN-γ KO mice induced apoptosis of activated CD4 T cells. IFN-γ–mediated apoptosis was abolished by depleting adherent cells or Mac-1+ spleen cells or by inhibiting nitric oxide synthase. Thus, IFN-γ is essential to a regulatory mechanism that eliminates activated CD4 T cells and maintains CD4 T cell homeostasis during an immune response.
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