APC FROM MICE HARBORING THE FILARIAL NEMATODE, BRUGIA-MALAYI, PREVENTCELLULAR PROLIFERATION BUT NOT CYTOKINE PRODUCTION

Specific T cell hyporesponsiveness and depressed antibody production i s a key feature of human infection with the filarial nematodes, Brugia malayi and Wuchereria bancrofti, Despite this immune suppression, res ponses indicative of T(h)2 subset activation are present, including un usually high levels of specific lgG4. We tested the possibility that i nfection with filarial nematodes causes a reduction in the co-stimulat ory or antigen-presenting capacity of macrophages resulting in a failu re to activate specific T cells, Adherent peritoneal exudate cells (PE G) from mice implanted with adult B. malayi were used to present antig en to the conalbumin-specific T cell clone, D10.G4. Proliferation of t he D10 cells at even background levels was completely blocked by the p resence of implant-derived adherent PEG. However, cytokine production by these cells in response to antigen was intact, and thus PEC from im planted mice are capable of functionally processing and presenting ant igen. The elicitation of a suppressive cell population was specific fo r live adults as cells from mice implanted with dead adult parasites e ffectively stimulated D10 proliferation. The block in cellular prolife ration is not due to the production of factors typically associated wi th macrophage suppression such as nitric oxide, prostaglandins or cata lase, These observations are consistent with the T cell hyporesponsive ness seen in human cases of patent Brugia infection and may provide a murine model for the immune suppression seen in lymphatic filariasis.