Interleukin 2 induces the expression of CD45RO and the memory phenotype by CD45RA+ peripheral blood lymphocytes

The CD45RA and CD45RO isoforms of the leukocyte common antigen identify functionally distinct "naive" and "memory" T cell subsets. While antigenic and mitogenic stimuli are known to initiate transition from the naive to memory state, little is known about the role of cytokines in this process. This report demonstrates that in vitro exposure of purified CD45RA+/CD45RO- peripheral blood lymphocytes (PBL) to interleukin 2 (IL-2) promotes their conversion to the CD45RA-/CD45RO+ phenotype. Conversion to CD45RO occurs for both the CD3+ and CD3-/CD56+ lymphocyte subsets, but occurs more rapidly, and at lower IL-2 concentrations, in the CD3-/CD56+ population. Expression of CD45RO was observed only in response to IL-2 and was not observed during long-term culture in IL-4, IL-6, or IL-7. We also examined the effect of IL-2 on the expression of adhesion molecules by T cells. The expression of CD2, CD11a, and CDw29 increased, and expression of Leu-8 (LAM-1) decreased, on cultured CD45RA+/CD45RO- cells after they converted to expression of CD45RO. In contrast, lymphocytes that remained CD45RA+/CD45RO- after 10 d in culture exhibited no change from their baseline adhesion molecule profile. Finally, to test the role of endogenous IL-2 during T cell activation we stimulated CD45RA+/CD45RO- PBL with immobilized anti-CD3 in the presence of neutralizing anti-IL-2 antibody and/or cyclosporin A. Both agents significantly reduced the expression of CD45RO and the effect of cyclosporin A was reversed by exogenous IL-2. We conclude that IL-2 promotes CD45RA+ cells to express the memory phenotype and is a mediator of CD45RO expression after stimulation of the T cell receptor/CD3 complex.