TY - JOUR

T1 - Cytokine production and apoptosis among T cells from patients under treatment for Plasmodium falciparum malaria

AU - Kemp, K

AU - Akanmori, B D

AU - Adabayeri, V

AU - Goka, B Q

AU - Kurtzhals, J A L

AU - Behr, C

AU - Hviid, L

N1 - Keywords: Animals; Antimalarials; Apoptosis; Child; Child, Preschool; Cytokines; Humans; Lymphocyte Activation; Malaria, Falciparum; Plasmodium falciparum; T-Lymphocyte Subsets

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 11882046

VL - 127

SP - 151

EP - 157

JO - Clinical and Experimental Immunology, Supplement

JF - Clinical and Experimental Immunology, Supplement

SN - 0964-2536

IS - 1

ER -