Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 192, Issue 1, Pages 123-128Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.192.1.123
Keywords
T lymphocytes; apoptosis; autoimmune diseases; anim disease models; knockout mice
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Funding
- NIAID NIH HHS [R29 AI041258-04, R29 AI041258-05] Funding Source: Medline
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Mice deficient in interferon (IFN)-gamma or IFN-gamma receptor develop progressive and fatal experimental autoimmune encephalomyelitis (EAE). We demonstrate that CD4 T cells lacking IFN-gamma production were required to passively transfer EAE, indicating that they were disease-mediating cells in IFN-gamma knockout (KO) mice. IFN-gamma KO mice accumulated 10-16-fold more activated CD4 T cells (CD4(+)CD44(hi)) than wild-type mice in thr central nervous system during EAE. CD4(+) CD44(hi) T cells in the spleen and central nervous system of IFN-gamma KO mice during EAE showed markedly increased in vivo proliferation and significantly decreased es vivo apoptosis compared with those of wild-type mice. IFN-gamma KO CD4(+)CD44(hi) T cells proliferated extensively to antigen restimulation in vitro and accumulated larger numbers of live CD4(+)CD44(hi) T cells. IFN-gamma completely suppressed proliferation and significantly induced apoptosis of CD4(+)CD44(hi) T cells responding to antigen and hence inhibited accumulation of live, activated CU4 T cells. We thus present novel in vivo and in vitro evidence that IFN-gamma may limit the extent of EAE by suppressing expansion of activated CD4 T cells.
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