THE REGULATORY ROLE OF ADENOSINE-ACTIVATED LYMPHOCYTE-T SUBSET ON THE IMMUNE-RESPONSE IN HUMANS .1. MITOGENIC RESPONSE AND PRODUCTION OF MEDIATORS

Human T lymphocytes, rerosetted with sheep erythrocytes [E] in the presence of adenosine, yield 2 subpopulations: a major one (ER), still capable of forming E rosettes; and a minor nonrosetting (ES) one. The 2 subpopulations differed in their proliferative responses to various mitogens. ER cells responded well to galactose oxidase (GO), soybean agglutinin (SBA), and phytohemagglutinin (PHA) but responded poorly to concanavalin A (Con A). The response of ES cells was poor to GO and SBA, intermediate to PHA, and significantly high to Con A. The different response of ER and ES subsets to Con A was not greatly affected by adherent cells, but an enhancing effect on the proliferation of ES cells to Con A was observed when prostaglandin synthesis was inhibited by indomethacin. Addition of ES cells to ER cells in a ratio of 1:5 resulted in an enhanced synergistic effect of Con A-induced proliferation. A soluble mitogenic factor released from Con A-activated T cells appeared involved in this enhanced proliferation. This factor (ESF) was produced only by the minor T-cell subpopulation which is sensitive to adenosine (ES). The induction of ESF was not dependent on the addition of adherent cells and required 72 h of incubation for its production. ESF was mitogenic to nonactivated and Con A-activated PBL as well as to T, ER, and ES subpopulations. Following incubation of ER cells with ESF, a suppressor factor (ERSF) was produced which abolished the mitogenic activity of ESF. Differences between these factors and a known mediator like interleukin-2 (IL-2) and suppressor factors are discussed.