T cell receptor-triggered activation of intraepithelial lymphocytes in vitro.

Intraepithelial lymphocytes (IEL) of the mouse small intestine were examined for their potential to respond to TCR signalling . Purified IEL subsets were activated using mAbs specific for CD3, TCRor TCRγ&. Thy-1IEL, regardless of TCR type, proliferated equally well in response to anti-TCR mAb with or without exogenous IL-2. In contrast, Thy-1 TCR, CD8 IEL required exogenous IL-2 for proliferation. No such requirement was observed for Thy-1 TCRγ& IEL proliferation. IEL proliferation in the absence of added IL-2 was due to an IL-2 secretion/IL-2 receptor (IL-2R) autocrine pathway, since mAbs specific for IL-2 and IL-2R inhibited IEL proliferation. Thy-1 CD8 CD4CD8 IEL were unresponsive to TCR-induced proliferation but exhibited high levels of cytolytic activity upon TCR-triggerlng. Thy-1 non-cytolytic IEL were induced to express Thy-1 and cytolytlc activity following activation . In addition, the involvement of the co-stimulatory molecule CD28 in IEL activation was tested. CD28 was weakly expressed by fresh IEL and anti-CD28 mAb had no effect on TCR-triggered proliferation. However, anti-TCR stimulation increased CD28 expression on a subset of TCR IEL and the addition of anti-CD28 mAb resulted in increased IL-2 production, but not in increased proliferation. Our results indicate that IEL, including the purported extrathymlc CD8 subset, can respond to TCR-driven signals via proliferation and/or cytolytlc activity. [ABSTRACT FROM PUBLISHER]