Precocious expression of T cell functional response genes in vivo in primitive thymocytes before T lineage commitment

The genes encoding effector molecules of mature T cells, IL-2, perforin andIL-4, were found to be expressed in vivo in the most primitive subsets ofthymocytes of adult mice. These subsets have previously been identified bytheir cell surface markers and by their expression of other Tlineage-associated genes. While IL-2, perforin and IL-4 are expressed indistinct patterns, all three are expressed before the induction of RAG-1and pre-TCR alpha mRNA expression, and are confined to subsets of cellsthat apparently have not yet undergone commitment to the T lineage. Thus,expression of T cell response genes appears to be one of the earliestmarkers of lymphocyte differentiation. Activation events marked by CD69induction occur in these early cell types, but the response gene expressionby these cells is separable from CD69 expression. IL-2 and perforin areinduced again much later in thymocyte development, during TCR-dependentrepertoire selection. At those stages, IL-2 protein and RNA levels per cellare higher, but the fraction of cells expressing IL-2 appears to be muchlower than in the most immature stages. In addition, a striking feature ofthe immature populations is the robust IL-2 expression by presumptiveimmature NK cells. These findings are discussed in terms of thedevelopmental origins of lineage specificity in T cell response generegulation.