Transient expression of IL-2 receptor precedes the differentiation of immature thymocytes

Abstract

The growth of mature T lymphocytes after activation by antigen is regulated by the binding and endocytosis of interleukin-2 (IL-2)^1,2. In the thymus, ∼50% of adult thymocytes that carry neither the CD4 nor the CD8 antigen and day 14–15 fetal CD4^–8^– thymocytes express receptors for IL-2(IL-2R)^3–5. The CD4^–8^– (double-negative) subpopulation of thymocytes contains the precursors of cells that can differentiate along an unknown pathway into thymocytes bearing either CD8 or CD4, with the characteristics of mature T lymphocytes^6,7. The basis for IL-2R expression by double-negative thymocytes is unclear as they appear to lack a functional T-cell receptor/CD3 complex through which activation of peripheral T cells is mediated⁸. The argument for a role for IL-2 in thymocyte differentiation has also been complicated by conflicting reports on the inability^9–12 or capability^4,13 of double-negative thymocytes to respond to IL-2 in vitro. At present, both the nature of the stimuli within the thymic micro-environment which induce IL-2R expression and its relevance to thymocyte differentiation are not known. We show here that the IL-2R-bearing subset has a greater potential to differentiate into phenotypically mature T lymphocytes than do IL-2R-negative thymocytes. In addition, progeny of IL-2R-negative donor cells transiently express IL-2R in the thymuses of adoptive hosts before generating CD8 and/or CD4-positive thymocytes. These results identify the IL-2R-positive cells as a more differentiated double-negative thymocyte subset on the pathway to mature T lymphocytes.