CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel.
BACKGROUND
Chronic schistosomiasis is associated with T cell hypo-responsiveness and immunoregulatory mechanisms, including induction of regulatory T cells (Tregs). However, little is known about Treg functional capacity during human Schistosoma haematobium infection.


METHODS
CD4+CD25hiFOXP3+ cells were characterized by flow cytometry and their function assessed by analysing total and Treg-depleted PBMC responses to schistosomal adult worm antigen (AWA), soluable egg antigen (SEA) and Bacillus Calmette-Guérin (BCG) in S. haematobium-infected Gabonese children before and 6 weeks after anthelmintic treatment. Cytokines responses (IFN-γ, IL-5, IL-10, IL-13, IL-17 and TNF) were integrated using Principal Component Analysis (PCA). Proliferation was measured by CFSE.


RESULTS
S. haematobium infection was associated with increased Treg frequencies, which decreased post-treatment. Cytokine responses clustered into two principal components reflecting regulatory and Th2-polarized (PC1) and pro-inflammatory and Th1-polarized (PC2) cytokine responses; both components increased post-treatment. Treg depletion resulted in increased PC1 and PC2 at both time-points. Proliferation on the other hand, showed no significant difference from pre- to post-treatment. Treg depletion resulted mostly in increased proliferative responses at the pre-treatment time-point only.


CONCLUSIONS
Schistosoma-associated CD4+CD25hiFOXP3+Tregs exert a suppressive effect on both proliferation and cytokine production. Although Treg frequency decreases after praziquantel treatment, their suppressive capacity remains unaltered when considering cytokine production whereas their influence on proliferation weakens with treatment.
Centre de Recherches Médicales de Lambaréné (CERMEL), BP118 Lambaréné, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany.
Yvonne
Y
Schmiedel
Centre de Recherches Médicales de Lambaréné (CERMEL), BP118 Lambaréné, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany; Departement de Parasitologie-Mycologie, Faculté de Médecine, Université des Sciences de la Santé, BP 4009, Libreville, Gabon.
Ghyslain
G
Mombo-Ngoma
Centre de Recherches Médicales de Lambaréné (CERMEL), BP118 Lambaréné, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany; Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Lucja A
LA
Labuda
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Jacqueline J
JJ
Janse
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Brechje
B
de Gier
Centre de Recherches Médicales de Lambaréné (CERMEL), BP118 Lambaréné, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany; Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Ayôla A
AA
Adegnika
Centre de Recherches Médicales de Lambaréné (CERMEL), BP118 Lambaréné, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany.
Saadou
S
Issifou
Centre de Recherches Médicales de Lambaréné (CERMEL), BP118 Lambaréné, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany.
Peter G
PG
Kremsner
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Hermelijn H
HH
Smits
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Maria
M
Yazdanbakhsh
D000293:Adolescent; D000871:Anthelmintics / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology; D002648:Child; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D010446:Peptide Fragments / Q000276:immunology; D011223:Praziquantel / Q000627:therapeutic use*; D012553:Schistosomiasis haematobia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000145:classification* / Q000276:immunology / Q000378:metabolism
D000871:Anthelmintics; D015704:CD4 Antigens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D010446:Peptide Fragments; C056725:CD4 (76-94); D011223:Praziquantel