title: Polyclonal expansion of peripheral gamma delta T cells in human Plasmodium falciparum malaria.
abstract: Plasmodium falciparum malaria in humans is associated with an increase in the percentage and absolute number of gamma delta T cells in the peripheral blood. This increase begins during the acute infection phase and persists for at least 4 weeks during convalescence. In the present study, 25 to 30% of the gamma delta T cells expressed HLA-DR antigens in vivo and in some patients they proliferated in response to further stimulation by purified human interleukin 2 in vitro. However, there was no in vitro proliferative response to various malarial antigens, including a 75-kDa heat shock protein and a 72-kDa glucose-regulated protein of P. falciparum during the acute infection phase. Cytofluorographic studies showed that although an increase of V delta 1- gamma delta T cells was largely responsible for the expansion of the total number of gamma delta T cells, there was also a proportional increase in V delta 1+ cells. These results were confirmed with anchored PCR and by DNA sequencing to characterize at the molecular level the set of T-cell receptor (TCR) delta mRNAs expressed in the peripheral blood of two patients with high levels of gamma delta T cells. In each case, most of the TCR delta mRNA transcripts corresponded to nonproductively rearranged delta genes (unrearranged J delta or near J delta spliced to C delta). In those sequences which did represent productively rearranged genes, most of the transcripts originated from a V delta 2/J delta 1 joining, as in normal individuals. A minority of transcripts originated from a V delta 1/J delta 1 rearrangement, and one originated from a V alpha 4/J delta 1 rearrangement. Polyclonal activation of gamma delta T cells was inferred from the extensive junctional diversity seen in the delta mRNAs analyzed. Expansion of a heterogeneous set of both V delta 1(-)- and V delta 1(+)-bearing T cells suggests that the elevated levels of gamma delta T cells seen during acute P. falciparum malaria arose from immune responses to multiple distinct parasite antigens or unidentified host factors.
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: M
authors.initials: M
authors.lastname: Ho
authors.forename: P
authors.initials: P
authors.lastname: Tongtawe
authors.forename: J
authors.initials: J
authors.lastname: Kriangkum
authors.forename: T
authors.initials: T
authors.lastname: Wimonwattrawatee
authors.forename: K
authors.initials: K
authors.lastname: Pattanapanyasat
authors.forename: L
authors.initials: L
authors.lastname: Bryant
authors.forename: J
authors.initials: J
authors.lastname: Shafiq
authors.forename: P
authors.initials: P
authors.lastname: Suntharsamai
authors.forename: S
authors.initials: S
authors.lastname: Looareesuwan
authors.forename: H K
authors.initials: HK
authors.lastname: Webster
authors.forename: J F
authors.initials: JF
authors.lastname: Elliott
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology*; D008969:Molecular Sequence Data; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta