Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease

Gullu Gorgun, Kenneth B. Miller, Francine M. Foss

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Extracorporeal photochemotherapy (ECP) has been shown to be an effective therapy for patients with acute and chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation, but its biologic mechanism is not understood. We reported that clinical response to ECP was associated not only with normalization of skewed CD4/CD8 ratios but also with an increase in CD3-/CD56+ natural killer cells and a decrease in the number of CD80+ and CD123+ circulating dendritic cells (DCs). To further elucidate the effects of ECP on activated lymphocyte subpopulations and the interaction between effector lymphocytes and antigen-presenting DCs, we isolated and characterized DC populations from patients with chronic GVHD undergoing ECP therapy. Antigen-presenting activity of DCs was measured as proliferation of antigen-stimulated autologous and allogeneic T cells by mixed-lymphocyte reaction (MLR). In MLR assays the proliferation of T cells was decreased in all 10 patients by a mean of 84% (range, 75%-95%; P ≤ .002) after a 2-day cycle of ECP and longitudinally over the 12-month course of therapy. Immunophenotypic analysis of DC populations revealed a preponderance of DC1 monocytic dendritic cells in all patients before the initiation of ECP. Nine of 10 patients demonstrated a shift from DC1 to DC2 and as a concordant shift from a predominantly Th1 (interleukin-2 [IL-2], interferon-γ) to Th2 (IL-4, IL-10) cytokine profile after ECP, and 8 of 10 had a clinical response to ECP. Our results suggest that ECP alters alloreactivity by affecting allo-targeted effector T cells and antigen-presenting DCs.

Original languageEnglish (US)
Pages (from-to)941-947
Number of pages7
JournalBlood
Volume100
Issue number3
DOIs
StatePublished - Aug 1 2002
Externally publishedYes

Fingerprint

Photopheresis
Graft vs Host Disease
Grafts
Dendritic Cells
Lymphocytes
T-cells
Antigens
Mixed Lymphocyte Culture Test
Antigen-Presenting Cells
T-Lymphocytes
CD4-CD8 Ratio
Interleukin-4
Interleukin-10
Interferons
Interleukin-2
Viral Tumor Antigens
Homologous Transplantation
Lymphocyte Subsets
Autoantigens
Assays

ASJC Scopus subject areas

  • Hematology

Cite this

Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease. / Gorgun, Gullu; Miller, Kenneth B.; Foss, Francine M.

In: Blood, Vol. 100, No. 3, 01.08.2002, p. 941-947.

Research output: Contribution to journalArticle

Gorgun, Gullu ; Miller, Kenneth B. ; Foss, Francine M. / Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease. In: Blood. 2002 ; Vol. 100, No. 3. pp. 941-947.
@article{a5b51963cc814263bcc6de70a0278157,
title = "Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease",
abstract = "Extracorporeal photochemotherapy (ECP) has been shown to be an effective therapy for patients with acute and chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation, but its biologic mechanism is not understood. We reported that clinical response to ECP was associated not only with normalization of skewed CD4/CD8 ratios but also with an increase in CD3-/CD56+ natural killer cells and a decrease in the number of CD80+ and CD123+ circulating dendritic cells (DCs). To further elucidate the effects of ECP on activated lymphocyte subpopulations and the interaction between effector lymphocytes and antigen-presenting DCs, we isolated and characterized DC populations from patients with chronic GVHD undergoing ECP therapy. Antigen-presenting activity of DCs was measured as proliferation of antigen-stimulated autologous and allogeneic T cells by mixed-lymphocyte reaction (MLR). In MLR assays the proliferation of T cells was decreased in all 10 patients by a mean of 84{\%} (range, 75{\%}-95{\%}; P ≤ .002) after a 2-day cycle of ECP and longitudinally over the 12-month course of therapy. Immunophenotypic analysis of DC populations revealed a preponderance of DC1 monocytic dendritic cells in all patients before the initiation of ECP. Nine of 10 patients demonstrated a shift from DC1 to DC2 and as a concordant shift from a predominantly Th1 (interleukin-2 [IL-2], interferon-γ) to Th2 (IL-4, IL-10) cytokine profile after ECP, and 8 of 10 had a clinical response to ECP. Our results suggest that ECP alters alloreactivity by affecting allo-targeted effector T cells and antigen-presenting DCs.",
author = "Gullu Gorgun and Miller, {Kenneth B.} and Foss, {Francine M.}",
year = "2002",
month = "8",
day = "1",
doi = "10.1182/blood-2002-01-0068",
language = "English (US)",
volume = "100",
pages = "941--947",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

TY - JOUR

T1 - Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease

AU - Gorgun, Gullu

AU - Miller, Kenneth B.

AU - Foss, Francine M.

PY - 2002/8/1

Y1 - 2002/8/1

N2 - Extracorporeal photochemotherapy (ECP) has been shown to be an effective therapy for patients with acute and chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation, but its biologic mechanism is not understood. We reported that clinical response to ECP was associated not only with normalization of skewed CD4/CD8 ratios but also with an increase in CD3-/CD56+ natural killer cells and a decrease in the number of CD80+ and CD123+ circulating dendritic cells (DCs). To further elucidate the effects of ECP on activated lymphocyte subpopulations and the interaction between effector lymphocytes and antigen-presenting DCs, we isolated and characterized DC populations from patients with chronic GVHD undergoing ECP therapy. Antigen-presenting activity of DCs was measured as proliferation of antigen-stimulated autologous and allogeneic T cells by mixed-lymphocyte reaction (MLR). In MLR assays the proliferation of T cells was decreased in all 10 patients by a mean of 84% (range, 75%-95%; P ≤ .002) after a 2-day cycle of ECP and longitudinally over the 12-month course of therapy. Immunophenotypic analysis of DC populations revealed a preponderance of DC1 monocytic dendritic cells in all patients before the initiation of ECP. Nine of 10 patients demonstrated a shift from DC1 to DC2 and as a concordant shift from a predominantly Th1 (interleukin-2 [IL-2], interferon-γ) to Th2 (IL-4, IL-10) cytokine profile after ECP, and 8 of 10 had a clinical response to ECP. Our results suggest that ECP alters alloreactivity by affecting allo-targeted effector T cells and antigen-presenting DCs.

AB - Extracorporeal photochemotherapy (ECP) has been shown to be an effective therapy for patients with acute and chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation, but its biologic mechanism is not understood. We reported that clinical response to ECP was associated not only with normalization of skewed CD4/CD8 ratios but also with an increase in CD3-/CD56+ natural killer cells and a decrease in the number of CD80+ and CD123+ circulating dendritic cells (DCs). To further elucidate the effects of ECP on activated lymphocyte subpopulations and the interaction between effector lymphocytes and antigen-presenting DCs, we isolated and characterized DC populations from patients with chronic GVHD undergoing ECP therapy. Antigen-presenting activity of DCs was measured as proliferation of antigen-stimulated autologous and allogeneic T cells by mixed-lymphocyte reaction (MLR). In MLR assays the proliferation of T cells was decreased in all 10 patients by a mean of 84% (range, 75%-95%; P ≤ .002) after a 2-day cycle of ECP and longitudinally over the 12-month course of therapy. Immunophenotypic analysis of DC populations revealed a preponderance of DC1 monocytic dendritic cells in all patients before the initiation of ECP. Nine of 10 patients demonstrated a shift from DC1 to DC2 and as a concordant shift from a predominantly Th1 (interleukin-2 [IL-2], interferon-γ) to Th2 (IL-4, IL-10) cytokine profile after ECP, and 8 of 10 had a clinical response to ECP. Our results suggest that ECP alters alloreactivity by affecting allo-targeted effector T cells and antigen-presenting DCs.

UR - http://www.scopus.com/inward/record.url?scp=0036682940&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036682940&partnerID=8YFLogxK

U2 - 10.1182/blood-2002-01-0068

DO - 10.1182/blood-2002-01-0068

M3 - Article

VL - 100

SP - 941

EP - 947

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -