CD2-CD58 interaction and the control of T-cell interleukin-12 responsiveness. Adhesion molecules link innate and acquired immunity.
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.
Gollob
J A
JA
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Ritz
J
J
D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D018801:CD2 Antigens / Q000502:physiology*; D018968:CD58 Antigens / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D018968:CD58 Antigens; D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma