Enhanced T cell proliferation in mice lacking the p85beta subunit of phosphoinositide 3-kinase.
Phosphoinositide 3-kinase activation is important for lymphocyte proliferation and survival. Disrupting the gene that encodes the major phosphoinositide 3-kinase regulatory isoform p85alpha impairs B cell development and proliferation. However, T cell functions are intact in the absence of p85alpha. In this study, we test the hypothesis that the related isoform p85beta is an essential regulatory subunit for T cell signaling. Unexpectedly, T cells lacking p85beta showed a marked increase in proliferation and decreased death when stimulated with anti-CD3 plus IL-2. Both CD4(+) and CD8(+) T cells completed more cell divisions. Transcriptional profiling revealed reduced levels of caspase-6 mRNA in p85beta-deficient T cells, which was paralleled by reduced caspase-6 enzyme activity. Increased T cell accumulation was also observed in vivo following infection of p85beta-deficient mice with mouse hepatitis virus. Together, these results suggest a unique role for p85beta in limiting T cell expansion.
Deane
Jonathan A
JA
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Trifilo
Matthew J
MJ
Yballe
Claudine M
CM
Choi
Sangdun
S
Lane
Thomas E
TE
Fruman
David A
DA
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D053178:Caspase 6; D020169:Caspases / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000502:physiology*; D051966:Phospholipase C gamma; D021122:Protein Subunits; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology
D007376:Interleukin-2; D021122:Protein Subunits; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; C505516:Casp6 protein, mouse; D053178:Caspase 6; D020169:Caspases; D002118:Calcium