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Immune Responses During Human Schistosomiasis Mansoni

III. Regulatory Effect of Patient Sera on Human Lymphocyte Blastogenic Responses to Schistosome Antigen Preparations^*

Daniel G. Colley, Sara E. Hieny, Richard K. Bartholomew AND Joseph A. Cook

The in vitro lymphocyte blastogenesis capabilities of patients with schistosomiasis mansoni were tested against phytohemagglutinin (PHA), Candida albicans extract, and soluble preparations of schistosome eggs (SEA), adult worms (SWAP), or cercariae (CAP). When patients' lymphocytes were cultured in medium which contained 5% human (homologous) normal (uninfected) serum, they responded well to PHA and Candida extract. The responses induced by SEA were maximal in patients with early Schistosoma mansoni infections, while reactivity against SWAP and CAP increased during chronic infection. These responses, induced by the schistosome-derived antigenic preparations, were suppressed if the homologous-normal serum supplement of the culture medium was replaced with either the patient's own (autologous) serum, or that of another S. mansoni patient. All sera were heat-inactivated (56°C/30 min) prior to use. In contrast, responses against the non-specific mitogen (PHA) and the unrelated antigen (Candida extract), were not altered by these changes of the serum supplementation of the media. The degree of suppression by patient serum was not changed by increasing the serum percentage in the medium from 5% to 25%. The suppressive effects of patient sera on responses induced by SEA and SWAP were increased in relationship to the duration of the serum donor's S. mansoni infection. Preincubation of lymphocytes in suppressive patient sera for 30 min at 37°C did not reduce the expected level of responsiveness if the cells were subsequently cultured in homologous-normal serum supplemented medium. The data indicate that during S. mansoni infection patients develop serum component(s) which specifically interfere with the responsiveness of their lymphocytes in regard to certain schistosome-derived antigenic preparations. The immunoregulatory events described could participate in the modulation of immunopathology, the maintenance of chronic adult worm survival, and the prevention of full expression of protective immune responses.

Accepted for publication March 12, 1977.

^* These investigations were principally supported by The Rockefeller Foundation (Grant #RF 74084) and the Research and Control Department of the Ministry of Health, Government of St. Lucia, the Overseas Development Administration Scheme R2108, and in part by USPHS Grant AI 11289 and the Veterans Administration Hospital, Nashville, Tennessee 37203.

External Staff, British Medical Research Council; seconded to The Rockefeller Foundation.

Staff member of The Rockefeller Foundation.