Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparum.
Chronic helminth infections induce T-cell hyporesponsiveness, which may affect immune responses to other pathogens or to vaccines. This study investigates the influence of Treg activity on proliferation and cytokine responses to BCG and Plasmodium falciparum-parasitized RBC in Indonesian schoolchildren. Geohelminth-infected children's in vitro T-cell proliferation to either BCG or pRBC was reduced compared to that of uninfected children. Although the frequency of CD4(+)CD25(hi)FOXP3(+) T cells was similar regardless of infection status, the suppressive activity differed between geohelminth-infected and geohelminth-uninfected groups: Ag-specific proliferative responses increased upon CD4(+)CD25(hi) T-cell depletion in geohelminth-infected subjects only. In addition, IFN-gamma production in response to both BCG and parasitized RBC was increased after removal of CD4(+)CD25(hi) T cells. These data demonstrate that geohelminth-associated Treg influence immune responses to bystander Ag of mycobacteria and plasmodia. Geohelminth-induced immune modulation may have important consequences for co-endemic infections and vaccine trials.
Wammes
Linda J
LJ
Department of Parasitology, Leiden University Medical Center, Leiden, the Netherlands.
Hamid
Firdaus
F
Wiria
Aprilianto E
AE
de Gier
Brechje
B
Sartono
Erliyani
E
Maizels
Rick M
RM
Luty
Adrian J F
AJ
Fillié
Yvonne
Y
Brice
Gary T
GT
Supali
Taniawati
T
Smits
Hermelijn H
HH
Yazdanbakhsh
Maria
M
D001500:BCG Vaccine / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D006373:Helminthiasis / Q000276:immunology* / Q000469:parasitology; D006801:Humans; D007214:Indonesia; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D016778:Malaria, Falciparum / Q000276:immunology* / Q000382:microbiology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
D001500:BCG Vaccine; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma