Maturation of neonatal human CD4 T cells: III. Role of B7 co-stimulation at priming.
We previously reported that human naive CD4 T cells differentiate into effector cells producing type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-5, IL-10) cytokines after priming with anti-CD3 mAb presented on irradiated CD32-transfected mouse L fibroblasts, in the absence of exogenous cytokine. Here we first show that the CD32 L fibroblasts act not only by cross-linking anti-CD3 mAb but also by providing a B7-mediated co-stimulation signal which is required for the activation of naive T cells. Using a selected anti-CD3 mAb (64.1) we next demonstrate that colligation of CD3 and CD28 with soluble mAb is sufficient to activate highly purified naive CD4 T cells for proliferation, IL-4 mRNA expression, IL-4 secretion, and maturation into IL-4- and IL-5-producing cells. Finally, we show that the intensity of B7 co-stimulation at priming markedly affects the lymphokine-producing phenotype of primed cells. Indeed, cells primed on CD32-B7 double L transfectants produce much more IL-4 and IL-5 and slightly less IFN-gamma than those primed on CD32 L cells. The enhanced IL-4/IL-5-producing capacity of cells primed on CD32-B7 L fibroblasts may be related to increased IL-4 production during priming. It is suggested that the maturation of naive T cells along the Th2 or Th1 pathway may be regulated by the level of B7 expressed on APC.
Yang
L P
LP
Allergy Research Laboratory (M4211-K), Centre de Recherche Louis-Charles Simard, Notre-Dame Hospital, University of Montreal, Quebec, Canada.
Demeure
C E
CE
Byun
D G
DG
Vezzio
N
N
Delespesse
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D015847:Interleukin-4 / Q000096:biosynthesis; D007739:L Cells; D008213:Lymphocyte Activation; D051379:Mice; D010641:Phenotype; D017452:Receptors, IgG / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D017452:Receptors, IgG; D015847:Interleukin-4