The relationship between human helper and suppressor factors to a streptococcal protein antigen.

Abstract

Abstract Helper and suppressor functions were studied in parallel in human lymphocytes to a protein antigen isolated from Streptococcus mutans. Because all subjects examined have antibodies to this common oral microorganism, the hypothesis was tested that natural sensitization to S. mutans might have induced in vivo specific helper and/or suppressor cells. Specific helper or suppressor factors were released in vitro with a range of doses of the streptococcal antigen (SA) and the factors were assayed for their ability to enhance or suppress antibody-forming cells to DNP-SA in cooperative cultures with mouse spleen cells. A differential dose response of predominantly 1000 ng of the SA was found between the helper function of HLA-DRw6 and DR4 lymphocytes. The suppressor activity showed a reciprocal relationship to helper activity, so that with DRw6 lymphocytes, help was elicited with 1 to 10 ng of SA and suppression with 100, 1000, and 10,000 ng of SA; however, DR4 lymphocytes released helper activity with 1000 ng SA and suppressor activity with lower and higher doses of SA. The resulting dose-response pattern of suppression-help-suppression resembled that recorded for low-zone and high-zone tolerance with an intermediate zone of immunity. The 1000 ng dose shift in helper activity, within a broad range of suppression, seems to be dependent on the HLA-DR locus. The effect of depletion of helper or suppressor cells was then investigated by killing these with the monoclonal T4 or T8 antisera and complement. This revealed that helper cells will release helper factor over the entire test range of doses of SA (1 to 10,000 ng) in suppressor cell-depleted cultures. Conversely, suppressor cells will release suppressor factor over the entire dose range of SA in helper cell-depleted cultures. The results suggest that although isolated human helper and suppressor cells are each capable of responding to a broad range of doses of SA, in unseparated lymphocytes helper and suppressor lymphocytes have a reciprocal controlling function on antibody formation. The coexistence of specific helper and suppressor functions demonstrated here in man is consistent with the findings in mice.