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Positive regulation of human T cell activation by Gi2 proteins and interleukin‐8
Author(s) -
Lippert Eric,
Jacques Yannick,
Hermouet Sylvie
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.67.5.742
Subject(s) - biology , microbiology and biotechnology , interleukin 2 , lymphocyte activation , t cell , immunology , cytokine , immune system
We investigated whether pertussis toxin (PT)‐sensitive heterotrimeric Gi proteins (G i1 , G i2 , G i3 ) are involved in the regulation of TCR‐induced activation of human T cells. First, Gi proteins were inactivated by PT: pretreatment with PT of purified blood T lymphocytes before CD3 cross‐linking inhibited cell proliferation (‐71.1 ± 22.0%, P < 0.001), production of interleukin‐2 (IL‐2; ‐47.3 ± 12.6%, P = 0.008), and expression of CD25 (‐24.6 ± 11.7%, P < 0.001) and CD69 (‐25.7 ± 9.0%, P < 0.001). Then, to identify which of the three Gi was involved, G i1 , G i2 , and G i3 proteins were specifically inactivated by stably transfecting dominant‐negative mutated forms of their α subunit in Jurkat cells. After activation, IL‐2 production and CD69 expression were inhibited only in cells expressing inactive G i2 . We then studied the effects of interleukin‐8 (IL‐8), a CXC‐chemokine with receptors coupled to G i2 and produced in an autocrine fashion by activated T cells. Although its effects varied among donors, exogenous IL‐8 stimulated proliferation and CD25 expression (up to, respectively, 200 and 77%) of PB T lymphocytes in response to CD3 activation, in a PT‐sensitive manner. IL‐8 also stimulated IL‐2 production (by up to 42%) and CD69 expression, although weakly (+27%). Anti‐human IL‐8 antibody inhibited proliferation (‐43%) and CD25 up‐regulation (‐45%) of activated T lymphocytes. In summary, several major responses of human T lymphocytes to TCR‐mediated activation are regulated by G i2 proteins, which for this function can be activated by IL‐8 in an autocrine manner.