DIFFERENTIAL-EFFECTS OF IL-10 ON PROLIFERATION AND CYTOKINE PRODUCTION OF HUMAN GAMMA/DELTA AND ALPHA/BETA T-CELLS

Gamma/delta TCR bearing T lymphocytes represent a T-cell subset whose functional relevance remains unclear. Nevertheless these T cells may play a role in the early immune reponse against bacteria. Until now the regulatory mechanisms on this response have not been investigated. The study described here evaluated the immunoregulatory effects of Interleukin-10 on gamma/delta and alpha/beta TCR-positive T-cell clones and freshly isolated peripheral-blood mononuclear cells (PBMC). IL-10 has been shown previously to inhibit lectin and antigen-induced proliferation and cytokine production by alpha/beta T cells. The results outlined below show that rhIL-10 strongly inhibits lectin-induced production of IFN-gamma, TNF-alpha, IL-2, and to a lesser degree proliferation and IL-4 production of both T-cell subsets. As IL-IO did not inhibit proliferation but at the same time strongly suppressed cytokine production in various experiments, the hypothesis that it could function as a growth factor for human T cells as has been described for murine thymocytes was tested. The data demonstrate that, although the gamma/delta T-cell clones tested do not produce IL-10 they can use it as a growth factor in combination with IL-2, IL-4 or alone. Furthermore, IL-10 has the same properties on human alpha/beta T-cell clones and PBMC. In summary, it is shown that IL-10 has pleiotropic effects on gamma/delta and alpha/beta TCR(+) T cells by inhibiting lectin-induced cytokine production and by acting as a growth factor for these cells alone or in combination with IL-2 or IL-4.