CD40 ligand is a T cell growth factor.
CD40 ligand (CD40L) is a 33-kDa type II membrane glycoprotein induced on T cells upon activation. CD40L has previously been shown to induce proliferation of resting B cells, immunoglobulin (Ig) secretion from B cells cultured with cytokines and cytokine secretion and tumoricidal activity from monocytes. In this report CD40L is shown to be stimulatory for human T cells, inducing CD25 (p55 IL-2R) and CD40L expression on resting peripheral blood T cells, enhanced expression of these molecules and CD69 on CD3-activated cells and secretion of interferon-gamma, tumor necrosis factor-alpha and interleukin (IL)-2 from T cells cultured in the presence of a sub-mitogenic concentration of phytohemagglutinin A (PHA). Furthermore, stimulation with CD40L induces proliferation of CD3- or PHA-activated T cells of blood, tonsillar or thymic origin. A similar proliferative response is observed with CD4+ and CD8+ T cells and this effect is largely IL-2 independent. A soluble construct of the extracellular domain of the CD40L has similar activity to that of membrane-expressed ligand in the induction of T cell surface antigens and proliferation. The results presented here taken together with the various activities ascribed for CD40L on B cells and monocytes demonstrate that CD40L has pleiotropic biological activity for cells of the hemopoietic lineage.
Armitage
R J
RJ
Department of Cellular Immunology, Immunex Research and Development Corporation, Seattle WA 98101.
Tough
T W
TW
Macduff
B M
BM
Fanslow
W C
WC
Spriggs
M K
MK
Ramsdell
F
F
Alderson
M R
MR
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D017252:CD3 Complex / Q000276:immunology; D019013:CD40 Antigens; D023201:CD40 Ligand; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D017252:CD3 Complex; D019013:CD40 Antigens; D007376:Interleukin-2; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand