Functional significance of Tac antigen expressed on activated human T lymphocytes: Tac antigen interacts with T cell growth factor in cellular proliferation.

Abstract

Cultured human T cells (CTC), which are grown in conditioned medium containing T cell growth factor (TCGF), proliferate in response to TCGF. It has been shown that an antigen (Tac) defined by a monoclonal antibody, termed anti-Tac antibody, is expressed on human T cells activated by mitogens or antigens and CTC grown in the presence of TCGF. To elucidate the functional significance of Tac antigen expressed on activated T cells, we studied the effect of anti-Tac antibody on TCGF-dependent proliferation of CTC. The addition of anti-Tac antibody strongly inhibited the proliferation of CTC induced by TCGF. This inhibition was observed only when the antibody was added at the early phase of culture, but not when the addition of the antibody was delayed beyond 24 hr of culture. Seven-day-old PHA-induced T cell blasts, but not fresh peripheral blood lymphocytes, were able to absorb TCGF activity in conditioned medium, as assessed by the DNA synthesis of CTC. When PHA-induced blasts were treated with anti-Tac antibody before absorption, their capacity to absorb TCGF activity was almost completely eliminated. In contrast, absorption of TCGF by PHA-induced blasts was not significantly reduced even when they were pretreated with other monoclonal antibodies (anti-Ia, OKT9, or OKT10) with specificity for antigens expressed on activated T cells. Based on the view that TCGF interacts with activated T cells via specific membrane receptors, these observations suggested that anti-Tac antibody might specifically block the binding of TCGF to the corresponding membrane binding sites, resulting in the inhibition of TCGF-dependent proliferation of CTC. Tac antigen expressed on activated T cells seems to participate in responding process of activated T cells to TCGF.