Premium
Persistent CD3‐Crosslinking Down‐Regulates Interleukin‐2 Responsiveness in Interleukin‐2‐Competent Cloned T Cells: the Possible Involvement of Protein Kinase C
Author(s) -
LANDEWÉ R. B. M.,
DIJKMANS B. A. C.,
VERDONK M.J. A.,
BREEDVELD F. C.,
DAHA M. R.,
MILTENBURG A. M. M.
Publication year - 1996
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1996.d01-280.x
Subject(s) - protein kinase c , cd3 , interleukin 2 , clone (java method) , biology , microbiology and biotechnology , activator (genetics) , receptor , t cell , t cell receptor , signal transduction , endocrinology , immunology , antigen , biochemistry , cd8 , immune system , dna
To investigate the regulation of interleukin‐2 (IL‐2) responsiveness of T cells, a human CD4 + T‐cell clone with constitutive expression of IL‐2 receptors was stimulated with recombinant IL‐2 (rIL‐2) in the presence or absence of immobilized anti‐CD3 monoclonal antibodies (αCD3 imm MoAb). Incubation of T cells with αCD3 imm MoAb decreased IL‐2‐induced proliferation which could not be ascribed to the modulation of IL‐2 receptor expression nor to cell death. Phorbol‐myristate‐acetate (PMA), an activator of protein kinase C (PKC), also induced down‐regulation of IL‐2 responsiveness. The αCD3 sol MoAb, inducing Ca 2+ ‐mobilization without activating PKC, did not inhibit IL‐2 responsiveness whereas cyclosporine A (CsA), a drug that inhibits the Ca 2+ ‐dependent activation pathway, did not prevent the induction of IL‐2 hyporesponsiveness induced by αCD3 imm MoAb. It is concluded that modulation of IL‐2 responsiveness of T cells via the T‐cell receptor/CD3 complex (TCR/CD3) may be mediated by a PKC‐activating signal.