Modulation of the host response in human schistosomiasis. IV. Parasite antigen induces release of histamine that inhibits lymphocyte responsiveness in vitro.

Abstract

Several mechanisms underlying the suppression of in vitro lymphocyte transformation responses to parasite antigens in human schistosomiasis have been previously described, but the role that immediate hypersensitivity reactions may have in regulating these lymphocyte transformation responses has been little explored. Using Hypaque-Ficoll-separated peripheral blood mononuclear cells (PBMC) from patients with schistosome infections, we found that histamine release could be demonstrated routinely in lymphocyte cultures challenged with adult worm, egg, or cercarial antigens. Release occurred within 1 hr of stimulation, and histamine persisted in the cultures for 6 days at levels of 10(-6) to 10(-7) M. That such concentrations were capable of suppressing LT responses in vitro was shown by the addition of exogenous histamine to modified PBMC culture systems from 10 normal individuals and eight patients with Schistosoma mansoni or Schistosoma mekongi infections. Responses to phytohemagglutinin, streptokinase-streptodornase, and tetanus were equivalently suppressed in both groups (50.8 +/- 6% in normals and 55.9 +/- 6.2% in patients), and the doses required for maximal suppression were similar. Passage of PBMC from infected patients over nylon wool, in addition to removing adherent suppressor cells, also markedly reduced the number of histamine-containing basophils (74 +/- 4.5% removed). The enhanced responsiveness to parasite antigen by PBMC depleted by nylon wool passage was abrogated by the addition of exogenous histamine to the cultures. These results indicate that in routine PBMC cultures 'nonspecific' lymphocyte suppression by histamine liberated from basophils in an antigen-specific fashion may help to account for the specific suppression of lymphocyte responses to parasite antigens so characteristic of patients with schistosome and other helminth infections.