Several studies are in progress aimed at determining the growth, differentiation, and cellular interactions involved in T cell development and in the inductive signals and selective mechanism which shape the mature T cell antigen repetoire. Mice treated in utero with anti-IL-2 receptor antibodies do not produce mature T cells in the fetal thymus and fail to express any TcRAlphamRNA in cortical-type thymocytes. Also the majority of proliferating cells in the early fetal thymus express IL-2 and IL-2R mRNA. The importance of the IL-2 and IL-2R to T cell development was also demonstrated in studies using PMA and ionomycin which promotes growth, IL-2 secretion, and differentiation to a mature phenotype with TcRAlphamRNA of the early adult and fetal thymocytes. Antibodies to the IL-2R block this growth and differentiation. No mature T cell antigen receptor or T3 was expressed in cells differentiated in response to PMA and ionophore. However, when the same cells are stimulated to grow in vitro using a combination of IL-1, IL-2, IL-3, and other factors, 100% T3+ cells develop by either selection or differentiation, a proportion of which express a mature phenotype (Lyt2+, L3T4-). The cells do not express the Alpha, Beta heterdimic TcR on their surface but instead express a Gamma, Gamma structure. This is the first demonstration of chain expression at the protein level in the mouse. The chain expressed on these cells has yet to be characterized. A cell with the same phenotype and TcR structure is first obtained in a minor subpopulation of day 15 fetal and in immature adult thymocytes. A study using in situ hybridization has revealed the ontogenetic expression of six important T cell genes at much earlier time points than was previously possible. More data have been obtained on rearrangements, nonconventional rearrangements, and of differential V region useage in fetal and immature adult thymocytes or in hybrids resulting from using these cells. Also studies are in progress of the T3 components and on the phosphorylation of these components as a result of activation.
