Nine rhesus monkeys with chronic Brugian filariasis and 3 uninfected controls were used in this project. Peripheral blood mononuclear cells (PBMC) from 3 infected animals responded to Brugia malayi adult antigen (BmA) (responder monkeys, RM) in vitro and cells from 6 of them did not (nonresponder monkeys, NRM). We have shown in this annual report that the polarization of the cellular response in RM and NRM monkeys seems to be due to an imbalance in the mRNA expressions of Th1 (IL-2 and IFN- ) and Th2 (IL-4 and IL-10) cytokine genes. As a continuation to understanding the mechanisms of T-cell unresponsiveness to filarial anitgens in these animals, we determined, by ELISA, the production of the secreted IL-2 and IFN- proteins in cultures of PBMC that had or had not been exposed to BmA or to Con A, and by flow cytometry, the expression of IL-2 receptor (IL-2R) on T cells in these cultures. IL-2 and IFN- were produced in BmA cultures of only 1 of 6 NRM. In contrast, IL-2 and IFN- were produced in similar cultures of 2 of 3 and in all 3 of 3 RM monkeys, respectively, correlating with the mRNA expression of these cytokine genes in these cultures. Neither IL-2 or IFN- were detected in antigen cultures of the 3 control animals. Both IL-2 and IFN- were significantly produced in Con A cultures of all animals. Assessment of the state of activation of these cells showed a significant increase in the percentage of T cells bearing IL-2R in BmA cultures of RM but not in those of NRM or control monkeys suggesting, less activated T cells in antigen cultures from the latter groups of animals. The density of IL-2R expressed on T cells in BmA cultures also were assessed by looking at the mean channel fluorescence intensity. There was an increase in the density of IL-2R on T cells in antigen cultures of both RM and NRM animals, but not on T cells of the control animals. The percentage of T cells in Con A cultures expressing IL-2R and the density of these IL-2R on T cells were similar for all animals. These results show an up-regulation of the expression of IL-2R on T cells in antigen cultures of RM and NRM monkeys. However, the percentage of T cells bearing IL-2R were down-regulated in antigen cultures of only NRM monkeys suggesting, a lower frequency of activated T cells in antigen cultures of NRM. The data suggest that the lack of production of the Th1 cytokines (IL-2 and IFN- ) and the down regulation of IL-2R on T cells in BmA cultures could be the cause of the unresponsiveness of PBMC from NRM monkeys to BmA in vitro.
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