Immunoregulatory T lymphocytes in man. Soluble antigen-specific suppressor-inducer T lymphocytes are derived from the CD4+CD45R-p80+ subpopulation

Abstract

Regulation of the immune response in man is largely dependent on interactions between cells of the cluster designation 4+ (CD4+) helper/inducer sublineage and the CD8+ suppressor/cytotoxic sublineage. When cultured with autologous antigen-primed CD4+ lymphocytes, CD8+ cells differentiate into suppressor T cells (Ts) that specifically inhibit the response of fresh autologous CD4+ cells to the priming antigen only. The current study was undertaken to analyze the roles in this suppressor circuit of subpopulations of the CD4+ sublineage distinguished from one another on the basis of their binding (or lack of binding) to monoclonal antibodies against molecules p80 (Leu8) and CD45R (p220/Leu18/2H4). When examined for the proliferative responses to alloantigenic stimuli, each of the four: CD4+p80+, CD4+p80-, CD4+CD45R+, and CD4+CD45R- populations proliferated vigorously, synthesized interleukin 2 (IL-2) and interferon and released soluble IL-2 receptors. However, the responses to soluble antigens such as Candida and diphtheria toxoid were exhibited by CD4+CD45R-, CD4+p80+, and CD4+p80- cells, but not by CD4+CD45R+ cells. When examined for their ability to induced CD8+ Ts in the Candida-driven suppressor-induction culture system, only CD4+p80+ and CD4+CD45R- cells induced strong suppression. Further, when CD4+CD45R- cells were separated into CD4+CD45R-p80+ and CD4+CD45R-p80- subpopulations, despite the ability of both subpopulations to respond to Candida, only CD4+CD45R-p80+ cells induced autologous CD8+ Ts. Activated CD8+ Ts suppressed not only proliferation but also the release of soluble IL-2 receptors by autologous antigen-activated CD4+ cells. Thus, the antigen-specific suppressor-inducer T cells appear to be derived from the CD4+CD45R-p80+ (Leu3+, Leu8+, 2H4-) subpopulation of the CD4+ sublineage.