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, perfori n and IL-4, were found to be expressed in vivo in the most primitive s ubsets of thymocytes of adult mice, These subsets have previously been identified by their cell surface markers and by their expression of o ther T lineage-associated genes, While IL-2, perforin and IL-4 are exp ressed in distinct patterns, all three are expressed before the induct ion of RAG-1 and pre-TCR alpha mRNA expression, and are confined to su bsets of cells that apparently have not yet undergone commitment to th e T lineage, Thus, expression of T cell response genes appears to be o ne of the earliest markers of lymphocyte differentiation, Activation e vents marked by CD69 induction occur in these early cell types, but th e response gene expression by these cells is separable from CD69 expre ssion, IL-2 and perforin are induced again much later in thymocyte dev elopment, during TCR-dependent repertoire selection, At those stages, IL-2 protein and RNA levels per cell are higher, but the fraction of c ells expressing IL-2 appears to be much lower than in the most immatur e stages, In addition, a striking feature of the immature populations is the robust IL-2 expression by presumptive immature NK cells, These findings are discussed in terms of the developmental origins of lineag e specificity in T cell response gene regulation.