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Relative roles of T‐cell receptor ligands and interleukin‐2 in driving T‐cell proliferation
Author(s) -
Chakrabarti Ranjana,
Kumar Sanjeev,
Chakrabarti Rabindranath
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(20000101)76:1<37::aid-jcb5>3.0.co;2-6
Subject(s) - cell growth , microbiology and biotechnology , t cell , t cell receptor , ionomycin , stimulation , interleukin 2 , biology , receptor , il 2 receptor , endocrinology , immunology , biochemistry , immune system
Stimulation of T cells by the T‐cell receptor (TCR)/CD3 complex results in interleukin‐2 (IL‐2) synthesis and surface expression of the IL‐2 receptor (IL‐2R), which in turn drive T‐cell proliferation. However, the significance of the requirement of IL‐2 in driving T‐cell proliferation, when TCR stimulation itself delivers potential mitogenic signals, is unclear. We show that blocking of IL‐2 synthesis by Cyclosporin A (CsA) suppressed both the Concanavalin A (Con A)‐ and phorbol myristate acetate (PMA)/ionomycin‐induced proliferation of T cells. The latter is also inhibited by anti‐IL‐2R. Kinetic studies showed that T‐cell proliferation begins to become resistant to CsA inhibition by about 12 h and became largely resistant by 18 h of stimulation. PMA, the protein kinase C activator, enhanced Con A‐induced T‐cell proliferation if added only within first 12 h of stimulation, and not after that. Given the fact that, in the present study, TCR is downregulated within 2 h of Con A stimulation and T cells entered the S phase of cell cycle by about 18 h of stimulation, the above results suggest that TCR stimulation provides the initial trigger to the resting T cells, which allows the cells to traverse the first two third portions of G1 phase of cell cycle and become proliferation competent. IL‐2 action begins afterward, delivering the actual proliferation signal(s), allowing the cells to traverse the rest of G1 phase and enter the S phase of the cell cycle. J. Cell. Biochem. 76:37–43, 1999. © 1999 Wiley‐Liss, Inc.