IL-4-SECRETING AND IL-5-SECRETING LYMPHOCYTE POPULATIONS ARE PREFERENTIALLY STIMULATED BY PARASITE-DERIVED ANTIGENS IN HUMAN TISSUE INVASIVE NEMATODE INFECTIONS

Helminth infections in humans and animals are associated with strong T helper 2 (Th2) responses. To determine whether parasite-derived Ag pr eferentially expand a Th2-like cell population, a filter immunoplaque assay was used to enumerate the frequencies (F0) of PBMC and CD4+-enri ched PBMC from individuals with helminth infections secreting selected cytokines in response to parasite-derived (PAg) and nonparasite antig ens (NPAg). In 20 individuals with lymphatic filariasis, frequency ana lysis of PBMC secreting IL-4 and IFN-gamma indicated that the F0 of PA g-specific IL-4-secreting cel Is (geometric mean F0 (GM): 1/12,100) wa s 57-fold higher than the corresponding F0 of NPAg-reactive cells (GM: 1/692,000; p < 0.02). In marked contrast, the F0 of IFN-gamma-secreti ng cells responding to PAg (GM: 1/2,700) did not differ from those of cells specific for NPAg (GM: 1/3,400; p = 0.83). In another group of h elminth-infected individuals, the F0 of highly enriched CD4+ cells sec reting IL-4 and IL-5 in response to PAg (GMs: 1/2,600 and 1/5,600 CD4 cells, respectively) were also found to be significantly higher than those specific for NPAg (GMs: 1/291,000 and 1/303,000 CD4+; p < 0.05 a nd p < 0.01, respectively), whereas the corresponding F0 of IFN-gamma- and granulocyte-macrophage-CSF-secreting cells were equivalent for PA g and NPag. Furthermore, the proportion of PAg-specific IL-4- and IL-5 -secreting CD4+ cells relative to all cells secreting the given cytoki ne were approximately 29-fold higher than the proportion of NPAg-speci fic cells secreting these cytokines. Again, the corresponding proporti ons of Ag-specific IFN-gamma and GM-CSF-secreting CD4+ cells were equi valent for PAg and NPAg. Thus, in this ex vivo system, a circulating p opulation of IL-4- and IL-5-secreting (Th2-like) cells has been shown to exist in humans; PAg appears to expand these cells preferentially.