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CD2‐CD58 Interaction and the Control of T‐Cell Interleukin‐12 Responsiveness
Author(s) -
GOLLOB JARED A.,
RITZ JEROME
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb52656.x
Subject(s) - t cell , cytokine , microbiology and biotechnology , biology , interleukin 21 , interleukin 12 , antigen presenting cell , immune system , cytotoxic t cell , immunology , in vitro , biochemistry
Interleukin-12 is an antigen-presenting cell (APC)-derived cytokine that stimulates T helper cell type 1 (Th1) differentiation as well as proliferation, cytolytic activity, and IFN-gamma production among T and natural killer (NK) cells. By immunizing mice with activated T cells and screening for antibodies that could inhibit IL-12-induced proliferation, CD2 was identified as a regulator of T-cell IL-12 responsiveness. Antibodies specific for the adhesion domain of either CD2 or its primary ligand, CD58, inhibited the major functional responses of T cells to IL-12 without affecting the response to IL-2. This inhibition did not involve any alteration in IL-12 binding to T cells. The CD2-CD58 interaction between activated T cells and monocytes was found to be a critical factor in the modulation of T-cell IL-12 responsiveness, and experiments using CD58-transfected Chinese hamster ovary (CHO) cells, and stimulatory pairs of CD2 antibodies confirmed the key role of CD2 ligation in optimizing T-cell IL-12 signaling. These findings illustrate how APCs, through the differential expression of a specific adhesion molecule, can control the T-cell response to a cytokine independent of cytokine receptor expression. This has important implications for an understanding of Th1 development and the conditions required to link innate with acquired immune responses.