title: Cytokine production and apoptosis among T cells from patients under treatment for Plasmodium falciparum malaria.
abstract: Available evidence suggests that Plasmodium falciparum malaria causes activation and reallocation of T cells, and that these in vivo primed cells re-emerge into the periphery following drug therapy. Here we have examined the cytokine production capacity and susceptibility to programmed cell death of peripheral T cells during and after the period of antimalarial treatment. A high proportion of peripheral CD3+ cells had an activated phenotype at and shortly after time of admission (day 0) and initiation of therapy. This activation peaked around day 2, and at this time-point peripheral T cells from the patients could be induced to produce cytokines at conditions of limited cytokine response in cells from healthy control donors. Activated CD8hi and TCR-gammadelta+ cells were the primary IFN-gamma producers, whereas CD4+ cells constituted an important source of TNF-alpha. The proportion of apoptotic T cells was elevated at admission and peaked 2 days later, while susceptibility to activation-induced cell death in vitro remained increased for at least 1 week after admission. Taken together, the data are consistent with the concept of malaria-induced reallocation of activated T cells to sites of inflammation, followed by their release back into the peripheral blood where they undergo apoptotic death to re-establish immunological homeostasis as inflammation subsides. However, the high proportion of pre-apoptotic cells from the time of admission suggests that apoptosis also contributes to the low frequency and number of T cells in the peripheral circulation during active disease.
authors.affiliation: Centre for Medical Parasitology at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet) and Institute for Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark. kkcmp@rh.dk
authors.forename: K
authors.initials: K
authors.lastname: Kemp
authors.forename: B D
authors.initials: BD
authors.lastname: Akanmori
authors.forename: V
authors.initials: V
authors.lastname: Adabayeri
authors.forename: B Q
authors.initials: BQ
authors.lastname: Goka
authors.forename: J A L
authors.initials: JA
authors.lastname: Kurtzhals
authors.forename: C
authors.initials: C
authors.lastname: Behr
authors.forename: L
authors.initials: L
authors.lastname: Hviid
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D010963:Plasmodium falciparum / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology*
chemical_list: D000962:Antimalarials; D016207:Cytokines