CYTOKINE PROFILES FOR HUMAN V-GAMMA-9(-CELLS STIMULATED BY PLASMODIUM-FALCIPARUM() T)

V(gamma)9(+) T cells from malaria non-exposed donors make proliferativ e responses to Plasmodium falciparum on in vitro stimulation. V(gamma) 9(+) cells are strongly activated by components of the schizont stage of the parasite and by antigens released into the culture upon schizog ony, while CD4(+) V(gamma)9(-) cells are stimulated by the earlier sta ges of the parasite. Using reverse transcriptase-polymer ase chain rea ction (RT-PCR) we determined mRNA expression for 14 cytokines in highl y purified V(gamma)9(+) cells enriched by positive selection after in vitro stimulation with P. falciparum schizont antigens. Interferon-gam ma (IFN-gamma) and Tumor Necrosis Factor-alpha (TNF-alpha) were detect ed in all samples tested. The majority of samples also expressed TNF-b eta, transforming growth factor-beta (TGF-beta) and Interleukin-8 (IL- 8). Only occasional samples expressed IL-2, IL-5 and IL-10. Using the ELISPOT assay we found that a large fraction of the reactive V(gamma)9 (+) cells produced IFN-gamma and that gamma delta T cells are the majo r producers of IFN-gamma in cultures stimulated with schizont antigens . The majority of V(gamma)9(+) cells in these cultures also express th e membrane-bound form of TNF-alpha. Expression of these cytokines spea ks for a cytolytic and/or inflammatory role of gamma delta cells in th e response to malaria in non-exposed individuals.