Diminished Production of T Helper 1 Cytokines and Lack of Induction of IL-2R+T Cells Correlate with T-Cell Unresponsiveness in Rhesus Monkeys Chronically Infected withBrugia malayi

Abstract

Giambartolomei, G. H., Lasater, B. L., Villinger, F., and Dennis, V. A. 1998. Diminished production of T helper 1 cytokines and lack of induction of IL-2R+T cells correlate with T-cell unresponsiveness in rhesus monkeys chronically infected withBrugia malayi. Experimental Parasitology90, 77–85. The relationship between antigen-specific responsiveness, parasitic burden, and lymphatic pathology was investigated in nine rhesus monkeys with chronicBrugia malayiinfections. Specifically,in vitroproliferation, cytokine gene expression and production, IL-2R expression on T cells, microfilaria (mf) densities, and lymphedema were evaluated. PBMC from three animals (two mf− one mf+) proliferated in response to filarial antigen (responder monkeys, RM) and cells from six animals (5 mf+; one mf−) did not (nonresponder monkeys, NRM). All RM showed lymphedema and none of the NRM did. Antigen-specific IL-2 and IFN-γ (mRNA and protein) were induced in PBMC from all RM whereas PBMC from only one of six NRM responded with IL-2 and IFN-γ expression. IL-4 transcripts were induced in PBMC from two of three RM and in cells from all six NRM. IL-10 mRNA expression and protein production were induced in PBMC from two of three RM and in cells from five of six NRM. A marked increase in the frequency of IL-2R+T cells was observed in antigen-stimulated PBMC cultures of RM but not in those of NRM. The data show that diminished production of Th1 cytokines and lack of induction of IL-2R+T cells may contribute to the unresponsiveness of PBMC from NRM to filarial antigen. They also show that the polarization of immune responses and lymphatic pathology observed in rhesus monkeys is similar to that generally described in human lymphatic filariasis patients.