Our objectives are to delineate the mechanisms by which T cells regulate antibody responses to the type 2 antigens type III pneumococcal polysaccharide (S3) and polyvinylpyrrolidone (PVP). We found that detection of suppressor T cells (Ts) in mice given S3 or S3-SC was dependent on elimination of contrasuppressor T cells (Tcs). Tcs were found to be important for induction of S3 immune responses. These studies will determine how Tcs are activated and how they prevent supression of B cells by Ts. Regulatory interactions will be analyzed in vivo using defined Tcs and Ts populations. The role of B cells and Igh gene products will be defined using B cell deprived mice and by determining the influence of the priming environment on development of Igh restrictions of Tcs. The biological role of Tcs will be further evaluated by determining the ability of Tcs to influence the development of tolerance and to influence responses to S3 in immune defective (xid) mice. We will attempt to develop Tcs clones to more precisely assess Tcs heterogeneity and function. In other studies we found that PVP activated T helper cells (TH) and Ts in a dose dependent manner. Low doses of PVP preferentially activate TH and induce memory in B cells but do not activate B cells to produce antibody. In contrast, amounts of PVP which induce optimal IgM antibody responses do not induce memory in B cells and preferentially activate Ts which prevent expression of TH and suppress IgG antibody. We will attempt to determine the basis for activation of TH vs. TS by PVP and will determine how TH, Ts, Tcs and B cells interact to result in IgG memory. The influence of the priming environment on development of Igh restricted TH will be assessed. Responses will be assessed in irradiated mice repopulated with defined cell populations. We will also attempt to develop methods to assess some of these responses in vitro. Many currently available polysaccharide vaccines are poorly immunogenic. The assessment of the roles of Tcs and TH in immune responses to type 2 antigens could provide information which could be applicable for improving the immunogenicity of polysaccharides. Further understanding of the role of Tcs in immune responses and the mechanisms by which Tcs abrogate effects of Ts will also be important in devising approaches for improving immune function in situations where Ts might predominate, e.g. patients with tumors or immunodeficiency diseases.
