Cytokine production by mature and immature thymocytes.

Abstract

We have studied the ability of subpopulations of activated thymocytes to produce four cytokines (IL-2, IL-4, IFN-gamma and TNF-alpha) which are believed to play roles in T cell development. Supernatants from various thymocyte subsets activated with calcium ionophore and PMA were tested for these cytokines. All CD3hi thymocyte subsets (CD4+8-, CD4-8- and CD4-8+) produced high titers of these four cytokines except CD3+4-8+ thymocytes, which did not produce IL-4. In contrast, CD4+8+ thymocytes did not produce any detectable cytokines. CD3-4-8- thymocytes produced IL-2, IFN-gamma, and TNF-alpha (but not IL-4) when activated by calcium ionophore + PMA and IL-1. We then separated CD3-4-8- thymocytes into IL-2R+ and IL-2R-. CD3-4-8-IL-2R+ thymocytes only produced small amounts of IL-2 when activated with calcium ionophore + PMA + IL-1, whereas CD3-4-8-IL-2R- thymocytes did not require IL-1 to produce IL-2, IFN-gamma, and TNF-alpha. Finally, CD4-8+3- thymocytes (an immature population believed to be an intermediate between CD3-4-8- and CD4+8+ thymocytes) only produced marginally detectable levels of IL-2 upon stimulation with calcium ionophore, PMA, and the addition of IL-1 did not result in increased levels of cytokine production. These observations indicate discrete patterns of cytokine production by the subsets studied and suggest specific controls of cytokine gene expression during T cell development.