Interleukin-17-producing T-helper cells as new potential player mediating graft-versus-host disease in patients undergoing allogeneic stem-cell transplantation.
OBJECTIVE
Graft-versus-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem-cell transplantation, leading to significant mortality. Recently, T-helper (TH)-17 cells have been shown to play a central role in mediating several autoimmune diseases. The aim of our study was to investigate the relationship between TH-17 cells and GVHD occurring in transplanted patients.


METHODS
Blood samples were collected from 51 hematopoietic stem-cell transplantation patients and 15 healthy donors. Patients with GVHD were monitored for the presence of TH-17 cells by ELISPOT or flow cytometry in the peripheral blood and by confocal microscopy in GVHD lesions. Cytokine plasma levels were detected by ELISA.


RESULTS
An increased TH-17 population (up to 4.8% of peripheral blood CD4+T lymphocytes) was observed in patients with acute GVHD and (up to 2.4%) in patients with active chronic GVHD along with an inflammatory process. In contrast, the percentage of TH-17 cells drastically decreased in patients with inactive chronic GVHD. TH-17 cells consisted of both interleukin (IL)-17+/interferon (IFN)-gamma- and IL-17+/IFN-gamma+ subsets and expressed IL-23 receptor. Interestingly, IFN-gamma+ TH-17 cells were able to infiltrate GVHD lesions as observed in liver and skin sections. Moreover, the proportion of TH-17 was inversely correlated with the proportion of regulatory T cells observed in the peripheral blood and tissues affected by GVHD. Finally, we demonstrated a strong correlation between TH-17 levels and the clinical status of patients with GVHD.


CONCLUSIONS
These findings support the hypothesis that TH-17 are involved in the active phases of GVHD and may represent a novel cellular target for developing new strategies for GVHD treatment.
Dander
Erica
E
Centro Ricerca M. Tettamanti, Clinica Pediatrica Università degli Studi di Milano Bicocca, Monza, Italy.
Balduzzi
Adriana
A
Zappa
Greta
G
Lucchini
Giovanna
G
Perseghin
Paolo
P
Andrè
Valentina
V
Todisco
Elisabetta
E
Rahal
Daoud
D
Migliavacca
Maddalena
M
Longoni
Daniela
D
Solinas
Graziella
G
Villa
Antonello
A
Berti
Emilio
E
Mina
Pamela Della
PD
Parma
Matteo
M
Allavena
Paola
P
Biagi
Ettore
E
Rovelli
Attilio
A
Biondi
Andrea
A
D'Amico
Giovanna
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000097:blood; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood*; D008099:Liver / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000097:blood; D012867:Skin / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous; D055815:Young Adult
D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C515500:IL23R protein, human; D018836:Inflammation Mediators; D020381:Interleukin-17; D018123:Receptors, Interleukin; D007371:Interferon-gamma