In vitro induction of a contrasuppressor immunoregulatory network by polyclonally activated T cells derived from murine Peyer's patches

Abstract

Much evidence suggests that Peyer's patch (PP) lymphocytes are capable of mounting both humoral and cell-mediated immune responses to luminal antigenic stimuli. To shed further light on T-T and T-B cell interactions in gut mucosal immune-associated processes, we studied in vitro the effects of a variety of PP-derived concanavalin A (Con A)-activated immunoregulatory T-cell subsets on class-specific immunoglobulin (Ig) production by lipopolysaccharide (LPS)-activated PP-derived B cells. Particular attention was focused on induction of a contrasuppressor T-cell immunoregulatory network in the above in vitro system. Three types of immunoregulatory effector T cells, a helper T (Th) cell, a suppressor T (Ts) cell and a contrasuppressor T (Tcs) cell were developed and isolated. The results showed that B cell Ig production was under the regulation of these T cells, and the L3T4+ Lyt-2- T cell, which bound to Vicia villosa (VV), had a contrasuppressor effector function. In addition, a L3T4+ Lyt-2- VV- Ts inducer (Tsi) subset and a L3T4- Lyt-2+ VV- Ts effector subset also appeared to participate in the sequential development of the suppressor and, probably, contrasuppressor immunoregulatory networks, respectively. Thus, PP T cells are likely to execute their highly sophisticated immunoregulatory functions, not only in the helper and suppressor circuits but also in the contrasuppressor circuit in response to intraluminal non-specific stimuli. However, IgA isotype-specific Ig production appears to be controlled primarily by the isotype-specific helper circuit, not by the contrasuppressor circuit, in polyclonal LPS-stimulated gut mucosal immune responses.