Ligation of CD28 on resting T cells by its ligand B7 results in the induction of both Th1- and Th2-type cytokines.
It has been well documented that cross-linking CD28 with mAb can provide a potent costimulatory signal to T cells for the production of IL-2, IL-6, IFN-gamma, GM-CSF and TNF-alpha. Much less is known about the role of the CD28 molecule in the induction of Th2-type lymphokines such as IL-4, IL-5, and IL-10. So far, only limited data are available about the secretion of IL-2, IL-6, IFN-gamma, and GM-CSF by T cells when using B7 as the natural ligand for CD28. We investigated whether B7-CD28 ligation can result in the secretion of Th2-type cytokines using 3T6 mouse fibroblasts transfected with human CD32 (Fc gamma RIIa high-responder allele, 3T6-CD32 cells) or with both CD32 and B7 (3T6-CD32/B7 cells). It was found that upon stimulation through the TCR/CD3 complex, B7-CD28 interaction not only results in the production of cytokines of the Th1 type, but also gives rise to the production of large amounts of Th-2 type cytokines such as IL-4 and IL-10. In contrast to the production of IL-2, IFN-gamma, GM-CSF, and TNF-alpha, the production of IL-4 after co-stimulation with B7-CD28 interaction was restricted to CD45RO+ memory T cells. In addition, the production of IL-4 after co-stimulation by B7-CD28 interaction was not influenced by the addition of IFN-gamma. The production of IFN-gamma was not affected by IL-4, but was slightly inhibited by IL-10.(ABSTRACT TRUNCATED AT 250 WORDS)
Walter
H
H
Department of Immunology, Innogenetics N.V. Ghent, Belgium.
Schepensn
S
S
Van Wauwe
J
J
de Boer
M
M
D000818:Animals; D018122:B7-1 Antigen / Q000494:pharmacology*; D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018122:B7-1 Antigen; D018106:CD28 Antigens; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor