CD40 ligand acts as a costimulatory signal for neonatal thymic gamma delta T cells.
The stimulatory requirements for T cells bearing gamma delta T cell receptors are distinct from those of alpha beta T cells. We have analyzed the ability of the CD40 ligand (CD40L) to activate neonatal thymic gamma delta T cells. CD40L is expressed on activated T cells and has been shown to induce B cell proliferation and Ig secretion as well as monocyte activation. We now demonstrate that, in the presence of an anti-TCR-gamma delta Ab, CD40L is able to induce the proliferation of neonatal thymic gamma delta cells. The presence of CD40L also leads to enhanced expression of a variety of activation-associated Ag including CD25, CD69, CD44, and Ly6C. In addition to proliferation, CD40L induces lectin-mediated cytolytic activity in thymic gamma delta T cells as well as the production of IFN-gamma and TNF-alpha. We were unable to detect IL-2 or IL-4 production in response to CD40L, and Ab-blocking studies indicate that the mechanism of activation appears to involve IL-1 but is independent of IL-2, IL-4, and IL-7. These results suggest that, in addition to its effects on B cells and monocytes, CD40L can costimulate the activation of thymic gamma delta T cells.
Ramsdell
F
F
Department of Immunobiology, Immunex Research and Development Corporation, Seattle, WA 98101.
Seaman
M S
MS
Clifford
K N
KN
Fanslow
W C
WC
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D019013:CD40 Antigens; D003602:Cytotoxicity, Immunologic; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
D000906:Antibodies; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D019013:CD40 Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma