Functional heterogeneity of helper T cells: two distinct helper T cells are required for the production of T cell growth factor.

A rat monoclonal antibody, obtained after immunization with cells from a cytolytic, TCGF-dependent T cell clone, was found to react with 10 to 20% of murine splenic and lymph node cells and with 65 to 70% of thymocytes. Addition of this antibody to normal spleen cell cultures, or cytotoxic elimination of the cells recognized by the antibody before culture, resulted in the abolishment or profound inhibition of the Con A-induced proliferative responses. The antibody did not react with or inhibit the proliferating, TCGF-reactive T cells, but it inhibited lectin-dependent TCGF production. An analysis of this inhibition, using purified cell populations and the macrophage-derived factor LAF, demonstrated that the cell removed by antibody cytotoxicity was neither the macrophage nor the TCGF-producing T cell, indicating that this antibody eliminates a second helper T cell required for lectin-dependent production of LAF by the accessory cells. These results extend previous observations on the T cell dependence of Con A-induced LAF production and identify a fourth cell type involved in the collaborative processes leading to TCGF-dependent T cell proliferation.