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)