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Extracorporeal photochemotherapy is accompanied by increasing levels of circulating CD4+CD25+GITR+Foxp3+CD62L+ functional regulatory T-cells in patients with graft-versus-host disease.
Transplantation. 2007 Jul 15; 84(1):31-9.T

Abstract

BACKGROUND

Extracorporeal photochemotherapy (ECP) produces clinical improvements in refractory/resistant graft-versus-host disease (GvHD). Immunological mechanisms of ECP are still under investigation.

METHODS

We have evaluated the changes in frequency and immunophenotype of circulating regulatory T cells (T-regs) in 10 patients undergoing allogeneic hematopoietic stem cell transplantation, receiving ECP for acute (n=4) or chronic (n=6) GvHD. T-regs were monitored for expression of surface CD4, CD25, GITR, CD45RO, CD62L and intracytoplasmic Foxp3. T-regs were sorted by fluorescence-activated cell sorting to perform functional assays by interferon (IFN)-gamma enzyme-linked immunospot and real-time quantitative polymerase chain reaction (RQ-PCR) to measure Foxp3, transforming growth factor (TGF)-beta, and interleukin (IL)-10 mRNA.

RESULTS

ECP was accompanied by a significant increase of CD4+CD25+ T-regs after six procedures, increasing from 8.9% to 29.1% of total CD4 (P<0.05), with a simultaneous increase of glucocorticoid induced tumor necrosis factor receptor expression on CD4+CD25+ cells (from 15% to 40.8%, P<0.05). This increase was sustained after 12 procedures. T-regs expressed high levels of CD62L, CD45RO, and Foxp3. Sorted CD4+CD25+ T-regs were potently inhibitory toward the CD4+CD25- fraction, when matched with an allogeneic target (IFN-gamma secretion was reduced by 79%). Trans-well experiments showed that cell-to-cell contact was necessary to exert inhibitory activity. RQ-PCR revealed a significant expression of Foxp3 in CD4+CD25+ T-regs, but there was virtually no detection of TGF-beta and IL-10. GvHD improved in all patients, allowing tapering or discontinuation of immunosuppressive drugs.

CONCLUSION

Our study shows a time correlation between ECP and increasing percentages of circulating functional T-regs. Albeit suggestive, our results need to be confirmed on larger series to determine the actual role of T-reg in mediating the clinical effect of ECP.

Authors+Show Affiliations

Pediatric Department, University of Milano-Bicocca, San Gerardo Hospital, Milan, Italy. ettore.biagi@pediatriamonza.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17627234

Citation

Biagi, Ettore, et al. "Extracorporeal Photochemotherapy Is Accompanied By Increasing Levels of Circulating CD4+CD25+GITR+Foxp3+CD62L+ Functional Regulatory T-cells in Patients With Graft-versus-host Disease." Transplantation, vol. 84, no. 1, 2007, pp. 31-9.
Biagi E, Di Biaso I, Leoni V, et al. Extracorporeal photochemotherapy is accompanied by increasing levels of circulating CD4+CD25+GITR+Foxp3+CD62L+ functional regulatory T-cells in patients with graft-versus-host disease. Transplantation. 2007;84(1):31-9.
Biagi, E., Di Biaso, I., Leoni, V., Gaipa, G., Rossi, V., Bugarin, C., Renoldi, G., Parma, M., Balduzzi, A., Perseghin, P., & Biondi, A. (2007). Extracorporeal photochemotherapy is accompanied by increasing levels of circulating CD4+CD25+GITR+Foxp3+CD62L+ functional regulatory T-cells in patients with graft-versus-host disease. Transplantation, 84(1), 31-9.
Biagi E, et al. Extracorporeal Photochemotherapy Is Accompanied By Increasing Levels of Circulating CD4+CD25+GITR+Foxp3+CD62L+ Functional Regulatory T-cells in Patients With Graft-versus-host Disease. Transplantation. 2007 Jul 15;84(1):31-9. PubMed PMID: 17627234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracorporeal photochemotherapy is accompanied by increasing levels of circulating CD4+CD25+GITR+Foxp3+CD62L+ functional regulatory T-cells in patients with graft-versus-host disease. AU - Biagi,Ettore, AU - Di Biaso,Iolanda, AU - Leoni,Veronica, AU - Gaipa,Giuseppe, AU - Rossi,Vincenzo, AU - Bugarin,Cristina, AU - Renoldi,Giuliano, AU - Parma,Matteo, AU - Balduzzi,Adriana, AU - Perseghin,Paolo, AU - Biondi,Andrea, PY - 2007/7/14/pubmed PY - 2007/8/22/medline PY - 2007/7/14/entrez SP - 31 EP - 9 JF - Transplantation JO - Transplantation VL - 84 IS - 1 N2 - BACKGROUND: Extracorporeal photochemotherapy (ECP) produces clinical improvements in refractory/resistant graft-versus-host disease (GvHD). Immunological mechanisms of ECP are still under investigation. METHODS: We have evaluated the changes in frequency and immunophenotype of circulating regulatory T cells (T-regs) in 10 patients undergoing allogeneic hematopoietic stem cell transplantation, receiving ECP for acute (n=4) or chronic (n=6) GvHD. T-regs were monitored for expression of surface CD4, CD25, GITR, CD45RO, CD62L and intracytoplasmic Foxp3. T-regs were sorted by fluorescence-activated cell sorting to perform functional assays by interferon (IFN)-gamma enzyme-linked immunospot and real-time quantitative polymerase chain reaction (RQ-PCR) to measure Foxp3, transforming growth factor (TGF)-beta, and interleukin (IL)-10 mRNA. RESULTS: ECP was accompanied by a significant increase of CD4+CD25+ T-regs after six procedures, increasing from 8.9% to 29.1% of total CD4 (P<0.05), with a simultaneous increase of glucocorticoid induced tumor necrosis factor receptor expression on CD4+CD25+ cells (from 15% to 40.8%, P<0.05). This increase was sustained after 12 procedures. T-regs expressed high levels of CD62L, CD45RO, and Foxp3. Sorted CD4+CD25+ T-regs were potently inhibitory toward the CD4+CD25- fraction, when matched with an allogeneic target (IFN-gamma secretion was reduced by 79%). Trans-well experiments showed that cell-to-cell contact was necessary to exert inhibitory activity. RQ-PCR revealed a significant expression of Foxp3 in CD4+CD25+ T-regs, but there was virtually no detection of TGF-beta and IL-10. GvHD improved in all patients, allowing tapering or discontinuation of immunosuppressive drugs. CONCLUSION: Our study shows a time correlation between ECP and increasing percentages of circulating functional T-regs. Albeit suggestive, our results need to be confirmed on larger series to determine the actual role of T-reg in mediating the clinical effect of ECP. SN - 0041-1337 UR - https://www.unboundmedicine.com/medline/citation/17627234/Extracorporeal_photochemotherapy_is_accompanied_by_increasing_levels_of_circulating_CD4+CD25+GITR+Foxp3+CD62L+_functional_regulatory_T_cells_in_patients_with_graft_versus_host_disease_ L2 - http://dx.doi.org/10.1097/01.tp.0000267785.52567.9c DB - PRIME DP - Unbound Medicine ER -