In:
The Journal of Immunology, The American Association of Immunologists, Vol. 176, No. 10 ( 2006-05-15), p. 6004-6011
Abstract:
Using model tumor T cell lines, protein kinase C (PKC) α has been implicated in IL-2 cytokine promoter activation in response to Ag receptor stimulation. In this study, for the first time, PKCα null mutant mice are analyzed and display normal T and B lymphocyte development. Peripheral CD3+ PKCα-deficient T cells show unimpaired activation-induced IL-2 cytokine secretion, surface expression of CD25, CD44, and CD69, as well as transactivation of the critical transcription factors NF-AT, NF-κB, AP-1, and STAT5 in vitro. Nevertheless, CD3/CD28 Ab- and MHC alloantigen-induced T cell proliferation and IFN-γ production are severely impaired in PKCα−/− CD3+ T cells. Consistently, PKCα-deficient CD3+ T cells from OVA-immunized PKCα-deficient mice exhibit markedly reduced recall proliferation to OVA in in vitro cultures. In vivo, PKCα-deficient mice give diminished OVA-specific IgG2a and IgG2b responses following OVA immunization experiments. In contrast, OVA-specific IgM and IgG1 responses and splenic PKCα−/− B cell proliferation are unimpaired. Our genetic data, thus, define PKCα as the physiological and nonredundant PKC isotype in signaling pathways that are necessary for T cell-dependent IFN-γ production and IgG2a/2b Ab responses.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.176.10.6004
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2006
detail.hit.zdb_id:
1475085-5
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