A critical role for interleukin 4 in activating alloreactive CD4 T cells.
To generate antigen-specific responses, T cells and antigen presenting cells (APCs) must physically associate with each other and elaborate soluble factors that drive the full differentiation of each cell type. Immediately after T cell activation, CD4 T cells can produce both interferon gamma (IFN-gamma) and interleukin 4 (IL-4) before polarization into distinct T helper subsets. Inhibition of IL-4 during mixed allogeneic lymphocyte culture resulted in a defect in the ability of APCs to generate sufficient costimulatory signals for activation of alloreactive T cells. In vivo, a deficiency in IL-4 production inhibited the activation of alloreactive IL-2-, IL-4- and IFN-gamma-producing CD4 T cells in mice challenged with allogeneic skin grafts, resulting in prolonged skin graft survival. Thus, production of IL-4 by CD4T cells helps activate alloreactive T cells by affecting APC function.
Bagley
J
J
Transplantation Biology Research Center, Massachusetts General Hospital, MGH-East, Building 149, 13th Street, Boston, MA 02129, USA.
Sawada
T
T
Wu
Y
Y
Iacomini
J
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016038:Skin Transplantation / Q000276:immunology; D015854:Up-Regulation
D016207:Cytokines; D015847:Interleukin-4