The production of regulatory cytokines for thymocyte proliferation by murine thymic epithelium in vitro.

Two separate cultures of pure, morphologically distinct thymic epithelial cells have been generated and maintained in culture for one year (A.C. Nieburgs et al., Cell. Immunol. 90, 439-450, 1985). Supernatants from one of these cell lines, TECs, were examined for functional activity on thymocytes in vitro. These supernatants contained three distinct intercellular mediators, each capable of modulating thymocyte responses to T-cell mitogens. Enhancement of thymocyte proliferation to suboptimal doses of mitogen was associated with a factor that eluted in the 97,000-Da region on molecular sieve chromatography and was functionally and physicochemically distinct from interleukin-1 and interleukin-2 (IL-1 and IL-2). Suppression of the thymocyte response to optimal doses of mitogen was mediated by a 1000- to 5000-Da factor. These two intercellular components have different susceptibilities to heat treatments and are trypsin insensitive. In addition, thymic epithelial cells produced significantly high levels of prostaglandin E2 (PGE2) which also suppressed thymocyte responses to mitogen, but only at high doses of supernatant. These epithelial cell-derived enhancing and inhibitory effects on thymocytes could play a role in regulating intrathymic events.