Human and experimental animals infected with the filarial parasite Brugia malayi exhibit T-cell hyporesponsiveness. Parasite antigen(s) that may be involved in down regulating T-cell responses are not fully characterized. Earlier studies in our laboratory showed that 10 fg/ml of Brugia malayi excretory/secretory (E/S) antigen suppressed in vitro the Con A-induced blastogenic response of peripheral blood mononuclear cells (PBMCs) from naive rhesus monkeys (37-42% inhibition). In contrast only 5-15% suppression was obtained when 10 fg/ml B. malayi adult worm antigen (BmA) were used rather than E/S. However, an increment in the dose of BmA was able to increase the percent suppression of Con A-induced blastogenic response of PBMCs from normal rhesus monkeys. Cells (viability> 95%) treated with different concentrations of BmA (10, 20, 40 and 80 fg/ml) for five days were washed and subsequently co-cultured with freshly obtained autologous cells in the presence of Con A. These concentrations rendered an inhibition of 4, 6, 29 and 41% respectively. Co-cultures of naive cells and cells treated with 80 fg/ml of PBS extracts of microfilariae, female and male adult worms achieved an immunosuppression of 55%, 48% and 54% respectively. Those experiments also showed that the specific activity was increased in the extracts of adult male worms and was similar to that of E/S product (10 fg/m). In addition, the suppressive effect could be exerted on responses of PBMCs to antigens from Candida albicans and on the responses stimulated by a mixed lymphocyte reaction. BmA was fractionated by size exclusion HPLC and a fraction was obtained that was able to induce 30% suppression at a concentration of only 5 fg/ml. These results suggest that B. malayi worms contain a suppressive component that may be shed in their E/S products. Current studies are being conducted to further purify and biochemically characterize this component and also to determine the mechanism(s) of the BmA-E/S suppression on the T-cell response.
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