Caspase 3 is not essential for the induction of anergy or multiple pathways of CD8+ T-cell death.
T-cell death is a fundamental process that is intricately regulated at multiple phases during T-cell differentiation, tolerance induction and the decline of the immune response. Caspase 3 is a crucial molecule regulating both mitochondrial and death receptor apoptotic pathways and therefore we were interested in examining the role of caspase 3 in T cells. Using P14 and H-Y CD8(+) TCR-transgenic models, our analysis has shown that caspase 3 is not required for thymic negative selection. In addition, caspase 3 does not play a prominent role in the contraction phase following acute viral infection, nor clonal deletion of CD8(+) T cells under tolerizing conditions. Surprisingly, our studies demonstrate that caspase 3 was not required for the induction of CD8(+) T-cell anergy in vivo, contrary to published reports using CD4(+) T cells. Therefore, these results demonstrate that caspase 3 is not essential in CD8(+) T cells for multiple forms of thymic or peripheral tolerance, nor the contraction phase after an acute anti-viral response.
Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, ON, Canada.
Kiichi
K
Murakami
Nicole
N
Liadis
Janice
J
Sarmiento
Alisha R
AR
Elford
Minna
M
Woo
Linh T
LT
Nguyen
Tak W
TW
Mak
Pamela S
PS
Ohashi
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D053148:Caspase 3 / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D017635:Clonal Anergy / Q000276:immunology; D006182:H-Y Antigen / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000254:growth & development / Q000276:immunology
D006182:H-Y Antigen; D011948:Receptors, Antigen, T-Cell; D053148:Caspase 3