Search

The in vitro induction of an ovalbumin-specific human T cell suppressor factor is described (TsF120-OA). The antigen-specific suppressive component can be purified by affinity chromatography from supernatants derived from Marbrook-Diener type cultures of peripheral blood T cells stimulated with a high dose of ovalbumin. TsF120-OA suppresses the antigen-induced PFC formation of human blood B cells in vitro in an antigen-specific way. The target of TsF120-OA activity is shown to be the T helper cell. No genetic restriction in the action of the factor is observed.

Some immunochemical characteristics of a T-cell-derived ovalbumin (OA) antigen-specific helper (ThF120-OA) and a corresponding OA-specific suppressor effector factor (TsF120-OA) are described. These immunoregulatory molecules are retained by columns containing either the insolubilized antigen OA or the lectin ConA, or antibodies specific for the VH-region of immunoglobulins, for the beta 2-microglobulin or for Ia-framework determinants. Neither the helper factor nor the suppressor factor showed affinity for antisera specific for immunoglobulin isotypes. In search of a constant-region-like structure in factor molecules, antisera were raised in rabbits using ThF120-OA and TsF120-OA. The results show that antisera raised against ThF120-OA recognize one or more determinants of different antigenic specificities common to human ThF. This common structure is not species-specific since it is also recognized by rabbit antisera to mouse helper factor. It is absent, however, on human TsF120-OA. In the same way, human TsF120-OA was shown to interact with rabbit antisera to human (or murine) suppressor factors of different antigenic specificities, but not with anti-ThF.

We intended to investigate whether the suppression of antigen-induced antibody responses in vitro in man by T suppressor cells required contact of T suppressor cells with target cells or whether this effect was mediated by factors released by T suppressor cells. To this end supernatants of antigen-induced T suppressor cells were tested (by a plaque forming cell assay) for their capacity to suppress antibody responses of autologous and allogeneic human peripheral blood lymphocytes. We have shown that supernatants of antigen-specific T suppressor cells, designated as TsF24: a) can suppress an antibody response of autologous but not allogeneic lymphocytes to the inducing antigen; b) are antigen-specific in their effect; and 3) are produced by radiosensitive T cells. Furthermore, the target of the factor is a radiosensitive T cell. These findings taken together indicate that, in the generation of T-effector suppressor cells in man, T-T interactions occur, and in addition, that cellfree factors may be involved in these interactions.

Suppression of an antigen-specific plaque-forming cell response of human blood lymphocytes can be effected by T mu+ cells that have been primed previously by antigen in vitro for 6 days. While lacking the capacity to suppress the plaque-forming response directly, these primed T mu+ suppressor-inducer cells stimulate a subpopulation of unprimed T mu gamma- cells to differentiate to T gamma + suppressor-effector cells. The T mu+, T gamma+ and T mu gamma- subsets have been shown to be heterogeneous populations of cells. Therefore, the functionally defined T suppressor-inducer, -precursor and -effector cells were characterized by OKT monoclonal antibodies and by the capacity to form rosettes with autologous erythrocytes (ar+). Evidence will be presented that in vitro a T4+mu+ar- cell induces a T8+mu gamma-ar+ precursor cell to differentiate to a T8+gamma+ar- suppressor-effector cell. A similar T suppressor-effector cell can also be isolated directly from peripheral blood of normal donors.

The in vitro induction and assay of an ovalbumin-specific human T cell helper factor are described. Peripheral blood T cells, cultured with ovalbumin in a Marbrook-Diener system, produce an antigen-specific factor(ThF120-OA), which can be purified by affinity chromatography. The in vitro studies with ThF120-OA pointed out that in the production of the factor as well as in the factor-B cell interaction the adherent cell determines the genetic restriction. The results of kinetic studies on T helper activities demonstrated that Thf120-OA provides an auxiliary activity at various moments during the differentiation of the human peripheral B cell into an antibody-secreting cell. The observed differences in the mode of action of Th cells and Th factor are discussed.