title: Human gamma delta T cells that inhibit the in vitro growth of the asexual blood stages of the Plasmodium falciparum parasite express cytolytic and proinflammatory molecules.
abstract: The functional properties, regarding parasite growth inhibition in vitro, the cytotoxic potential and cytokine profiles of human gammadelta+ and alphabeta+ T cells, T-cell lines and clones stimulated with Plasmodium falciparum-antigen-or T-cell mitogen in vitro were investigated. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and specific primers, mRNA for the cytolytic molecules perforin, granzyme A and B, Fas and Fas ligand (FasL) were detected in both the gammadelta- and the alphabetaT cells. Despite this fact, only gammadeltaT cells inhibited, both Vdelta1+ and Vdelta2+, the in vitro growth of the asexual blood stages in a dose dependent manner. The inhibition required cell-to-cell contact and was not observed until the second parasite replication implied that the likely gammadeltaT-cell target was the extracellular merozoite or schizont. The failure of alphabetaT cells to inhibit the growth of the parasite suggests requirement of additional cytolytic molecules/signals or different receptor specificities exhibited by the gammadeltaT cells. Both the gammadelta- and alphabetaT cells expressed mRNA for a large number of cytokines. Interferon (IFN)-gamma, interleukin (IL) IL-5, IL-6, IL-8, tumour necrosis factor alpha (TNFalpha), tumour necrosis factor beta (TNF-beta)/lymphotoxin (LT) and T-cell growth factor beta-1 (TGF-beta1) were observed in all activated clones tested. No IL-3 was detected, while IL-1beta, IL-2, IL-4, IL-10 and GM-CSF were variably expressed. In conclusion, our data show that gammadeltaT cells in malaria nonimmune individuals inhibit the asexual blood stages of P. falciparum malaria, while similarly activated alphabetaT cells do not. Thus, it is likely that the gammadeltaT cells could play a mandatory role in the elimination of parasites and/or the regulation of the early immune response to malaria infection.
authors.affiliation: Department of Immunology, Stockholm University, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Troye-Blomberg
authors.forename: S
authors.initials: S
authors.lastname: Worku
authors.forename: P
authors.initials: P
authors.lastname: Tangteerawatana
authors.forename: R
authors.initials: R
authors.lastname: Jamshaid
authors.forename: K
authors.initials: K
authors.lastname: Söderström
authors.forename: G
authors.initials: G
authors.lastname: Elghazali
authors.forename: L
authors.initials: L
authors.lastname: Moretta
authors.forename: M
authors.initials: M
authors.lastname: Hammarström
authors.forename: L
authors.initials: L
authors.lastname: Mincheva-Nilsson
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D004912:Erythrocytes / Q000469:parasitology; D053222:Fas Ligand Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D053804:Granzymes; D006801:Humans; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D054353:Perforin; D010835:Phytohemagglutinins / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008222:Lymphokines; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019014:fas Receptor; D054353:Perforin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human