IN-VIVO CYTOKINE EXPRESSION IN THE THYMUS CD3(HIGH) HUMAN THYMOCYTES ARE ACTIVATED AND ALREADY FUNCTIONALLY DIFFERENTIATED IN HELPER AND CYTOTOXIC-CELLS

CD4 and CD8 are expressed on mutually exclusive T cell populations tha t can recognize peptides bound to class II and class I MHC Ags, respec tively. These populations have different functions and are different i n their capacity to produce cytokines. In this paper we demonstrate th at this functional differentiation occurs at the CD3(low)-CD3(high) tr ansitional stage: single positive mature CD4(+) thymocytes express IL- 2 mRNA in vivo, whereas CD8(+) thymocytes primarily express perforin. IL-2, perforin, and IFN-gamma mRNAs were almost absent in CD4(+)CD8(+) CD3(low) but were clearly detectable in CD4(+)CD8(+) CD3(high) cells, indicating that these genes are induced at the CD3(low)-CD3(high) tra nsitional stage. In contrast, IL-4 mRNA levels were highest in the pre cursor cells but dropped sharply at the CD3(low)-CD3(high) transitiona l stage. These data are consistent with and link two earlier observati ons, i.e., that activation occurs at the CD3(low)-CD3(high) transition and that functional differentiation in helper and cytotoxic cells is already accomplished in the single positive thymocytes. This activatio n may reflect positive selection and concomitant functional differenti ation into helper and cytotoxic T cells.