IL-4 and IL-5 secreting lymphocyte populations are preferentially stimulated by parasite-derived antigens in human tissue invasive nematode infections.
Mahanty, S.; King, C.L.; Kumaraswami, V.; Regunathan, J.; Maya, A.; Jayaraman, K.; Abrams John, S.; Ottesen Eric, A.; Nutman Thomas, B.
Journal of Immunology; 1993; 151; 3704-3711.
Helminth infections in humans and animals are associated with strong T helper 2 (Th2) responses. To determine whether parasite-derived Ag preferentially expand a Th2-like cell population, a filter immunoplaque assay was used to enumerate the frequencies (F o ) of PBMC and CD4 + -enriched PBMC from individuals with helminth infections secreting selected cytokines in response to parasite derived (PAg) and nonparasite antigens (NPAg). In 20 individuals with lymphatic filariasis, frequency analysis of PBMC secreting IL-4 and IFN- g indicated that the F o of PAg-specific IL-4 secreting cells (geometric mean F o (GM): 1/12, 100) was 57-fold higher than the corresponding F o of NPAg-reactive cells (GM: 1/692,000;p < 0.02). In marked contrast, the F o of IFN-g-secreting 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 helminth infected individuals, the F o of highly enriched CD4 + cells secreting 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 and p < 0.01, respectively), whereas the corresponding F o of IFN- g -and granulocyte-macrophage-CSF-secreting cells were equivalent for PAg and NPag. Furthermore, the proportion of PAg-specific IL-4 and IL-5 secreting CD4 + cells relative to all cells secreting the given cytokine were approximately 29-fold higher than the proportion of NPAg-specific cells secreting these cytokines. Again, the corresponding proportions of Ag-specific IFN-g-and GM-CSF-secreting CD4 + cells were equivalent for PAg and NPAg. Thus, in this ex vivo system, a circulating population of IL-4 and IL-5 secreting (Th2-like) cells has been shown to exist in humans; PAg appears to expand these cells preferentially.
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