Journal
JOURNAL OF IMMUNOLOGY
Volume 164, Issue 3, Pages 1286-1292Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.164.3.1286
Keywords
-
Categories
Funding
- NCI NIH HHS [P30CA16087] Funding Source: Medline
- NIAID NIH HHS [R01AI28900] Funding Source: Medline
Ask authors/readers for more resources
Lymphocytes derived from mice deficient in STAT1 showed reduced apoptosis and enhanced proliferation in vitro. To understand the involvement of STAT1 in the observed reduction in apoptosis, we examined the levels of caspase and bcl-2 family genes that are involved in cell survival and/or apoptosis, The levels of caspase 1 and 11, two enzymes involved in both cytokine protein processing and induction of apoptosis, were reduced in STAT1(-/-) cells compared with wild-type. However, the levels of bcl-2 genes were comparable in both mice, STAT1(-/-) cells also displayed an enhanced proliferation following TCR stimulation. This hyperproliferation could not be ascribed completely to the loss of IFN-gamma-mediated antiproliferation, First, similar phenotypes were also observed in fibroblasts and pre-B cells derived from STAT1(-/-) mice, which do not produce IFN-gamma, Second, comparisons with cells lacking the gene for IFN-gamma or with cells treated with neutralizing Abs to IFN-gamma only partially mimicked the STAT1(-/-) phenotype, Interestingly, the kinetics of degradation of p27(kip1), a CDK inhibitor, following TCR ligation were faster, and, concomitantly, the up-regulation of CDK2 kinase activity and protein levels were increased in stimulated T cells of STAT1(-/-) mice relative to those of wild-type mice. Furthermore, STAT1(-/-) animals were more susceptible to carcinogen-induced thymic tumors, a possible consequence of altered T cell growth and/or survival. These results demonstrate an essential role for STAT1 for lymphocyte survival and proliferation that is only partially dependent on IFN-gamma signaling.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available