Ligation of CD28 on resting T cells by its ligand B7 results in the induction of both Th1- and Th2-type cytokines
Walter, H.; Schepensn, S.; Van Wauwe, J.; de Boer, M.
European Cytokine Network 5(1): 13-21
1994
ISSN/ISBN: 1148-5493 PMID: 7519453 Document Number: 435735
It has been well documented that cross-linking CD28 with mAb can provide a potent co-stimulatory 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 (FcyRIIa high-responder allele, 3T6-CD32 cells) or with both CD32 and B7 (3T6-CD32/137 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 137-CD28 interaction was restricted to CD45RO+ memory T cells. In addition, the production of IL-4 after co-stimulation by 137-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. The addition of IL-10 to T cells co-stimulated by B7-CD28 strongly reduced the production of both TNF-alpha and GM-CSF. We have concluded that B7-CD28 interaction can provide the co-stimulatory signal for the production of both Th1- and Th2-type lymphokines.