The chemokine CCL18 generates adaptive regulatory T cells from memory CD4+ T cells of healthy but not allergic subjects.
The purpose of this study was to assess the direct effect of CCL18, a chemokine elevated in allergic diseases and induced by Th2 cytokines, on the polarization of human CD4(+) T cells. Purified human T cells from healthy subjects were pretreated or not with CCL18, and evaluated for cytokine production. CCL18-pretreated memory but not naive CD4(+) T cells exhibited an increased production of IL-10 (12.3 ± 2.6 vs. 5.6 ± 0.9 ng/ml for medium) and TGF-β1 but not IL-4, IFN-γ, and IL-17 compared with control cells. Pretreatment of highly purified CD4(+)CD25(-) memory T cells with CCL18 led to their conversion to CD4(+)CD25(+)Foxp3(+) regulatory T cells able to inhibit the proliferation of CD4(+)CD25(-) effector T cells by both cytokine and cell contact-dependent mechanisms. However, this regulatory effect of CCL18 was lost when T cells originated from allergic subjects in relation with a decreased binding of CCL18 to these cells [0.7 ± 0.3 mean fluorescence intensity (MFI)] as compared to those from healthy subjects (6.0 ± 1.7 MFI). This study is the first to define a chemokine that generates adaptive regulatory T cells from CD4(+)CD25(-) memory T cells. This mechanism appears defective in allergic patients and may underlie the decreased tolerance observed in allergic diseases.
Chang
Ying
Y
Institut National de Santé et de Recherche Médicale, Lille, France.
de Nadai
Patricia
P
Azzaoui
Imane
I
Morales
Olivier
O
Delhem
Nadira
N
Vorng
Han
H
Tomavo
Stanislas
S
Ait Yahia
Saliha
S
Zhang
Guizhen
G
Wallaert
Benoît
B
Chenivesse
Cécile
C
Tsicopoulos
Anne
A
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019742:Chemokines, CC / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
C111792:CCL18 protein, human; D019742:Chemokines, CC; D018793:Interleukin-13; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10