Activation of immature cortical thymocytes through the T11 sheep erythrocyte binding protein.

Two major pathways, the T cell receptor and the T11 alternate pathway, allow for T cell activation. In the human thymus, the T cell antigen receptor complex is reduced or absent on immature thymocytes, whereas the T11 glycoprotein is present at high cell surface density on all thymocytes. To determine whether activation through the T11 pathway induces similar or different changes in mature and immature thymocytes, we fractionated thymocytes according to their surface expression of the T3-T cell receptor (T3/Ti) complex. We report that two populations, one with high and one with low T3/Ti expression, can be activated through the T11 pathway to undergo nuclear activation and express IL 2 receptors. Moreover, in the absence of accessory cells, only the most mature population, expressing high T3 density, could be induced to proliferate, whereas the subset representing immature cortical thymocytes required accessory cells for proliferation. These findings suggest that the cellular microenvironment may have a critical role in regulating the activation of immature cortical thymocytes and that this cell population may not represent "nonfunctional" dead end cells, but rather a valid intermediate in human thymic differentiation.(12). represents the product of a separate thymocyte lineage that is destined for intrathymic death (1 3). In the present studies, we separated thymocytes on the basis of T3 antigen density into fractions with high T3 density (T3H,2 fractions with low T3 density (T3l. And fractions lacking detectablere activity with anti-T3 antibody (T3-). We show that both the T3H fraction, representing the most mature thymocytes, and the T3l population, representing the majority of T6+T4+T8+ thymocytes, can be activated through the T1 l pathway (14) to undergo nuclear activation and express IL 2 receptors. Furthermore, in the presence but not in the absence of accessory cells, the T3l population could be induced to proliferate. These results suggest hat immature cortical thymocytes, represented by the T3l population. Possess a number of capacities which are necessary for cells serving as intermediates int hymic ontogeny.