T cell proliferation induced by anti-CD3 antibodies: requirement for a T-T cell interaction

In the presence of interleukin 2 (IL2), soluble anti-CD3 monoclonal antibodies can stimulate highly purified normal T lymphocytes to proliferate. In these experiments HLADR+ T cells constituted 13 to 20% of the total cell population, and other HLADR+ cells, such as monocytes and B lymphocytes, constituted less than 1% of the population. When the HLADR+ T cells were removed from the total T cell population by cytofluorometric sorting, the residual HLADR- T cells failed to respond to soluble anti-CD3 plus IL2. When the separated HLADR+ T cells were recombined with the HLADR- T cells, a response was again found. This response was dependent on the dose of HLADR+ T cells added in the mixture. Irradiation individually of the HLADR+ and DR- T cells revealed that the proliferation in the cell mixture was predominantly, if not exclusively, by the HLADR- T cells. The ability of the HLADR+ T cells to provide a signal necessary to this proliferation was radioresistant. These data indicate that under the conditions of these experiments HLADR+ ("activated") T cells provide a signal necessary to the responsiveness of previously resting T cells.