Suppression of human lymphocyte mitogenesis mediated by phagocyte-released reactive oxygen species: comparative activities in normals and in chronic granulomatous disease.

Human blood monocytes and neutrophils stimulated in vitro with phorbol myristate acetate, N-formyl-L-methionyl-L-leucyl-L-phenylalanine, activated zymosan, or heat aggregated gamma-globulin were found to suppress lymphocyte mitogenic responses. In activated phagocyte-lymphocyte cocultures, both blast transformation and [3H]-thymidine incorporation were reduced while numbers of dead cells were increased, thus suggesting a cytolethal suppressive mechanism. Suppression was prevented by catalase but not by other oxygen radical scavengers nor by cyclooxygenase inhibitors, thus implicating H2O2 as the suppressive mediator. Activated monocytes and neutrophils but not lymphocytes released measurable quantities of H2O2 into cell supernatants. However, transfer of an inhibitory effect with these supernatants was not routinely achieved. Finally, as opposed to normals, lymphocyte blastogenesis in chronic granulomatous disease patients was not inhibited by their activated phagocytes. However, catalase -reversible suppression could be restored in cocultures of normal phagocytes and patient lymphocytes. In conclusion, these studies demonstrate a potentially important mechanism whereby activated phagocytes may alter lymphocyte reactivity.