Th17 immune responses contribute to the pathophysiology of aplastic anemia.
T helper type 17 (Th17) cells have been characterized based on production of interleukin-17 (IL-17) and association with autoimmune diseases. We studied the role of Th17 cells in aplastic anemia (AA) by isolating Th17 cells from patients blood (n = 41) and bone marrow (BM) mononuclear cells (n = 7). The frequency and total number of CD3(+)CD4(+)IL-17-producing T cells were increased in AA patients at presentation compared with healthy controls (P = .0007 and .02, respectively) and correlated with disease activity. There was an inverse relationship between the numbers of Th17 cells and CD4(+)CD25(high)FoxP3(+) regulatory T cells (Tregs) in the blood of AA patients. Concomitant with the classical Th1 response, we detected the presence of CD4(+) and CD8(+) IL-17-producing T cells in a mouse model of lymph node infusion-induced BM failure. Although anti-IL-17 treatment did not abrogate BM failure, early treatment with the anti-IL-17 antibody reduced the severity of BM failure with significantly higher platelet (P < .01) and total BM cell (P < .05) counts at day 10. Recipients that received anti-IL-17 treatment had significantly fewer Th1 cells (P < .01) and more Treg cells (P < .05) at day 10 after lymph node infusion. Th17 immune responses contribute to AA pathophysiology, especially at the early stage during disease progression.
de Latour
Regis Peffault
RP
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. peffaultdelatour@sls.aphp.fr
Visconte
Valeria
V
Takaku
Tomoiku
T
Wu
Colin
C
Erie
Andrew J
AJ
Sarcon
Annahita K
AK
Desierto
Marie J
MJ
Scheinberg
Phillip
P
Keyvanfar
Keyvan
K
Nunez
Olga
O
Chen
Jichun
J
Young
Neal S
NS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003710:Demography; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
D057134:Antibodies, Neutralizing; D020381:Interleukin-17; D007371:Interferon-gamma