Dk. Dalton et al., Interferon gamma eliminates responding CD4 T cells during mycobacterial infection by inducing apoptosis of activated CD4 T cells, J EXP MED, 192(1), 2000, pp. 117-122
In Mycobacterium bovis Bacille Calmette-Guerin (BCG)-infected wild-type mic
e, there was a large expansion of an activated (CD44(hi)) splenic CD4 T cel
l population followed by a rapid contraction of this population to normal n
umbers. Contraction of the activated CD4 T cell population in wild-type mic
e was associated with increased apoptosis of activated CD4 T cells. In BCG-
infected interferon (IFN)-gamma knockout (KO) mice, the activated CD4 T cel
l population did not undergo apoptosis. These mice accumulated large number
s 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 apop
tosis was abolished by depleting adherent cells or Mac-1(+) spleen cells or
by inhibiting nitric oxide synthase. Thus, IFN-gamma is essential to a reg
ulatory mechanism that eliminates activated CD4 T cells and maintains CD4 T
cell homeostasis during an immune response.