1358 Helper and Suppressor T Cell Activation by Pvp

Type 2 antigens such as polyvinylpyrrolidone (PVP), 1 type III pneumococcal polysaccharide ($3), and dinitrophenyl (DNP)-ficoll characteristically elicit antibody responses in mice that consist almost entirely of antibodies of the IgM and IgG3 isotypes (1-4). Type 2 antigens also are generally unable to prime mice to produce I gG 1 and IgG2 antibodies after secondary challenge, i.e. they are unable to prime for IgG memory responses (2, 5-8). The inability of these antigens to prime mice for IgG memory responses is presumably due, at least in part, to the fact that type 2 antigens generally do not activate antigen-specific helper T cells (Th), which have been shown (5, 9-14) to be required for the differentiation of B cells to IgG-producing memory B cells. For example, previous studies from this laboratory (5, 6, 14) showed that the type 2 antigen $3 could prime for IgG memory responses only if $3 was coupled to a carrier, horse red blood cells (HRBC), which could activate Th. These activated Th were required for the differentiation of B cells to IgG-producing B memory cells. In subsequent studies using PVP as antigen, it was shown (15, 16) that very low doses (0.0025 #g) of this type 2 antigen could prime mice for IgG memory responses nearly as effectively as a thymus-dependent (TD) form of PVP: PVP coupled to HRBC. By contrast, higher doses of PVP could not induce IgG memory responses; these amounts of PVP actually interferred with the induction of memory cells by PVPHRBC (15). Consistent with the premise that activation of Th was required to prime B memory cells, it was further shown (15, 16) that the low dose of PVP activated Th, while higher doses did not. This study further examines the requirements for activation of Th by PVP. The results indicate that higher doses of PVP can activate PVP-specific Th, but that these Th can only be detected when suppressor T cells (Ts) are eliminated. Thus, very low doses of PVP preferentially activate Th, whereas higher doses of PVP activate both Th and Ts, and the activity of the latter cells predominate in whole T cell populations. The implications of these findings for induction of IgG responses to type 2 antigens will be discussed.