The regulation of the expression of gp39, the CD40 ligand, on normal and cloned CD4+ T cells.
Studies have established that gp39, the ligand for CD40, induces B cell cycle entry and is involved in the initiation of the humoral immune response. Expression of gp39 has been observed on normal, activated CD4+ T cells, activated lymph node cells; an activated Th1 clone, and an activated Th2 clone. Anti-CD3-activated CD8+ T cells did not express gp39; however, CD8+ T cells activated with PMA/ionomycin expressed gp39. The kinetics of anti-CD3-induced gp39 expression on a T cell clone and on splenic CD4+ T cells showed that gp39 was detectable at 4 h after activation, reaching maximal levels between 6 to 8 h postactivation and returning to near resting levels between 24 to 48 h. Lymphokines modulated the expression of gp39 on activated T cells. Expression of gp39 was inhibited by IFN-gamma on activated Th1, Th2, and CD4+ T cells; whereas TGF-beta inhibited gp39 expression only on the Th2 clone studied. All other lymphokines tested were without substantial effect. Differences in the expression of gp39 on activated naive and memory T cells were observed, as well as differences in requirements for optimal gp39 expression on these subsets. There are correlations between gp39 expression and effector function; however, anti-CD3-activated splenic CD4+ cells that express gp39 did not exhibit effector function. A comparison of the relative numbers of molecules of gp39 shows that activated Th1 clones express at least 20-fold the number of gp39 molecules/cell compared with activated splenic CD4+ cells. This may imply that density of gp39 on the activated T cells plays an important role in determining effector function.
Roy
M
M
Graduate Program in Biochemistry, Dartmouth Medical School, Lebanon, NH 03756.
Waldschmidt
T
T
Aruffo
A
A
Ledbetter
J A
JA
Noelle
R J
RJ
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D017493:Leukocyte Common Antigens / Q000032:analysis; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D008024:Ligands; D008222:Lymphokines; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D016572:Cyclosporine; D017493:Leukocyte Common Antigens