Immunoregulatory T cell subpopulations in man: dissection by monoclonal antibodies and Fc-receptors.

Until now, most of the studies on regulatory T cells have been based on culture systems in which human peripheral blood cells are stimulated by polyclonal stimulators like Pokeweed Mitogen (PWM). Our present contribution, however, deals with T cell-mediated regulation of the antigen-induced B cell activation, which exclusively leads to an antigen-specific IgM production (Heijnen et al. 1979a). Some authors' reports on regulatory activities of T cells, as tested in systems using polyclonal stimulators, differ from ours. This may be due to: a) as a result of polyclonal stimulus, various types of regulatory T cells are activated at the same time b) in contrast to a primary antigen, a polyclonal stimulator induces a rapid proliferation of the various regulatory T cells c) a polyclonal stimulator induces the differentiation of B cells in various maturational stages, that might each require additional or different regulatory signals. For example, Thomas et al. (1981) have shown that freshly isolated T4+ cells can induce suppressor activity in unprimed T8+ cells in the presence of PWM, whereas T4+ cells, precultured for 24 h in the presence of PWM, can exert a suppressor activity themselves without an apparent need for T8+ cells. In the antigen-specific system, however, we have neither been able to detect T suppressor effector activity in a population of primed T4+ cells, nor been able to demonstrate T suppressor inducer activity in unprimed T4+ cells (Heijnen et al. 1982a). Therefore the state of activation of the total T4+ population will dictate the balance of the total T helper and T suppressor activity. As a result of proliferation induced by polyclonal mitogens, small subsets of regulatory T cells, which are functionally undetectable in the primary antigen-specific assay, can expand sufficiently to have a measurable effect. Thomas et al. (1980) have shown that the T4+ suppressor inducer cell in the PWM system is radio-sensitive, which is in contrast with our data in the antigen-specific system. This may imply that we are looking at different subsets of T suppressor inducer cells in these different systems, but it might also indicate that T suppressor inducer cells need to proliferate in order to be able to measurably regulate the large pool of responding cells generated in the PWM system. Apart from such quantitative effects, polyclonal B cell activators like PWM are capable of inducing the differentiation of B cells in various maturational stages (Kuritani & Cooper 1982, Stevens 1982, Peters & Fauci 1983). Since it is highly likely that the regulation of these various B cell subsets might require different regulatory signals, the PWM model might be a very complicated model to study regulatory effects of single T cell subsets.(ABSTRACT TRUNCATED AT 400 WORDS)