SPECIFIC T-CELL UNRESPONSIVENESS IN HUMAN FILARIASIS - DIVERSITY IN UNDERLYING MECHANISMS

In an attempt to overcome T cell unresponsiveness to filarial antigens , 65 individuals belonging to the three clinical groups of elephantias is patients, microfilaraemics, and asymptomatic amicrofilaraemics who exhibited unresponsiveness to Brugia malayi adult worm antigen (BmA) w ere studied. Peripheral blood mononuclear cells were co-cultured with antigen and one of the following reagents that have been reported to b e effective in reconstituting T cell proliferation: interleukin-2 (IL- 2), interleukin-7 (IL-7), anti-interleukin-4, anti-interleukin-10, ant i-CD2, anti-CD27, anti-CD28, indomethacin, phorbol myristate acetate ( PMA), or calcium ionophore (A23187). We were able to overcome antigen- specific unresponsiveness in only a minority of the individuals studie d. Co-culture with IL-2, IL-7, indomethacin and PMA were the only cond itions which resulted in enhanced proliferation to BmA in these indivi duals. In general, unresponsiveness in elephantiasis patients was easi er to reverse than in other clinical groups: in 50% of elephantiasis p atients, in 12.5% of microfilaraemics and in 20% of asymptomatic amicr ofilaraemics. The results indicate that more than one distinct immunol ogical mechanism may account for the antigen-specific unresponsiveness in individuals exposed to and infected with brugian filariasis.