1034 Antigen - Specific

Cooperation between thymus-derived (T) a lymphocytes and non-thymus-derived (B) lymphocytes has been shown to be necessary for the antibody response to protein antigens in experimental animals (1) and in man (2). Supernates of antigen-stimulated T cells can replace T cells for the in vitro antibody response by B cells (3). Two classes of T-ceU helper factors have been demonstrated in experimental animals: nonspecific helper factors and antigen specific helper factors. Nonspecific T-cell helper factors (NSF) behave like polyclonal B-cell activators. They trigger autologous as well as allogeneic B cells to proliferate and secrete antibodies against a variety of antigens (4). On the other hand, antigen-specific helper factors (ASF) induce B cells to produce antibody that is directed exclusively against the antigen used to elicit the T-cell helper activity (5). In mice, ASF can be absorbed on immunosorbent columns containing the antigen used to raise the factor as well as on immunosorbent columns containing antisera to Ia determinants expressed on the cells that produced the factor (6). It has been thus suggested that ASF contains an antigen-binding site as well as determinants encoded for by the Ia region of the major histocompatibility complex. Previous work in our laboratory has demonstrated that supernates of tetanus toxoid (TT)-stimulated human T cells contain a helper factor, termed lymphocyte mitogenic factor (LMF-TT) which induces proliferation, IgG synthesis, and specific ant i -TT antibody synthesis in autologous as well as allogeneic B cells (2). Further work identified the presence of NSF in these supernates (7). It was shown that supernates depleted of T T antigen by passage over ant i -TT immunosorbent columns were still capable of inducing proliferation and IgG synthesis in as much as 35-50% of B cells. Furthermore, NSF could induce specific antibody synthesis against T T as well as against an unrelated antigen such as diphtheria toxoid (DT) provided that second antigen was added to the T-cell cultures and provided the B-cell donor was immune to that antigen. The purpose of the present study was to identify ASF activity in the supernates of TT-st imulated human T lymphocytes.