Regulatory T cells and extracorporeal photochemotherapy: correlation with clinical response and decreased frequency of proinflammatory T cells.
BACKGROUND
Immune mechanisms of extracorporeal photochemotherapy (ECP) in refractory/resistant graft-versus-host disease (GvHD) are complex. We have previously analyzed the role of CD4CD25Foxp3 regulatory T cells (T-regs).


METHODS
In the current study, we have enlarged the size of the population (n=27; chronic GvHD=18, acute GvHD=9) for a median follow-up of 24 months. T-regs were monitored for CD4, CD25, glucocorticoid-induced tumor necrosis factor receptor (GITR), CD62L, CCR7, Foxp3, and STAT-5. Immune analysis by interleukin (IL)-17 Elispot was carried out on circulating T-helper CD4 cells secreting IL-17, a subset of T cells considered relevant in the pathogenesis of GvHD.


RESULTS
We confirm that ECP is accompanied by a significant increase of CD4CD25Foxp3GITRCD62LCCR7 T-regs. Sorted T-regs show augmented phosphorylation of STAT-5. Only ECP-responding patients demonstrate a raise of circulating T-regs, being mostly affected by chronic GvHD. Moreover, this phenomenon corresponds to a diminished secretion of IL-17.


CONCLUSIONS
In conclusion, our study shows that T-regs represent important immune mediators of the clinical benefits of ECP in patients affected by GvHD.
Pediatric Department, Laboratory of Cell Therapy Stefano Verri, University of Milano-Bicocca, San Gerardo Hospital, Monza (Milan), Italy. ettore.biagi@pediatriamonza.it
Iolanda
I
Di Biaso
Lucia
L
Di Maio
Cristina
C
Bugarin
Giuseppe
G
Gaipa
Erica
E
Dander
Adriana
A
Balduzzi
Matteo
M
Parma
Giovanna
G
D'Amico
Paolo
P
Perseghin
Andrea
A
Biondi
Ettore
E
Biagi
D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008730:Methoxsalen / Q000627:therapeutic use; D017893:Photopheresis; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D008730:Methoxsalen