Kinetics of IFN-γ and IL-17 Production by CD4 and CD8 T Cells during Acute Graft-versus-Host Disease
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Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-γ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 → BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 → BALB.B GVHD model, we showed that the production of IFN-γ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-γ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.
Abstract
Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-γ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 → BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 → BALB.B GVHD model, we showed that the production of IFN-γ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-γ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.
참고문헌 (34)
- Blazar, B. R., "Advances in graft-versus-host disease biology and therapy", Nat. Rev. Immunol, 12, pp.443~458 (2012)
- Shlomchik, W. D., "Graft-versus-host disease", Nat. Rev. Immunol, 7, pp.340~352 (2007)
- Filipovich, A. H., "National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of blood and marrow transplantation", Biol. Blood Marrow Transplant, 11, pp.945~956 (2005)
- Socie, G, "Acute graft-versus-host disease: from the bench to the bedside", Blood, 114, pp.4327~4336 (2009)
- Sun, Y., "Pathophysiology of acute graft-versus-host disease: recent advances", Transl. Res, 150, pp.197~214 (2007)
- Ferrara, J. L., "Pathophysiologic mechanisms of acute graft-vs.-host disease", Biol. Blood Marrow Transplant, 5, pp.347~356 (1999)
- Iclozan, C., "T helper17 cells are sufficient but not necessary to induce acute graft-versus-host disease", Biol. Blood Marrow Transplant, 16, pp.170~178 (2010)
- Yi, T., "Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease", Blood, 114, pp.3101~3112 (2009)
- Yang, Y. G., "Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12", J. Clin. Invest, 102, pp.2126~2135 (1998)
- Dong, C., "TH17 cells in development: an updated view of their molecular identity and genetic programming", Nat. Rev. Immunol, 8, pp.337~348 (2008)
- Antonysamy, M. A, "Evidence for a role of IL-17 in alloimmunity: a novel IL-17 antagonist promotes heart graft survival", Transplant. Proc, 31, pp.93~ (1999)
- Loong, C. C., "Evidence for the early involvement of interleukin 17 in human and experimental renal allograft rejection", J. Pathol, 197, pp.322~332 (2002)
- Serody, J. S., "The IL-17 differentiation pathway and its role in transplant outcome", Biol. Blood Marrow Transplant, 18, pp.S56~S61 (2012)
- Carlson, M. J., "In vitro-differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations", Blood, 113, pp.1365~1374 (2009)
- Kappel, L. W., "IL-17 contributes to CD4-mediated graft-versus-host disease", Blood, 113, pp.945~952 (2009)
- Yi, T., "Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease", Blood, 112, pp.2101~2110 (2008)
- Yen, H. R., "Tc17 CD8 T cells: functional plasticity and subset diversity", J. Immunol, 183, pp.7161~7168 (2009)
- Lai, H. Y., "Cytokine profiles in various graft-versus-host disease target organs following hematopoietic stem cell transplantation", Cell Transplant, 21, pp.2033~2045 (2012)
- Choi, E. Y., "Real-time T-cell profiling identifies H60 as a major minor histocompatibility antigen in murine graft-versus-host disease", Blood, 100, pp.4259~4265 (2002)
- Myung Geun Song, "In Vivo Imaging of Differences in Early Donor Cell Proliferation in Graft-Versus-Host Disease Hosts with Different Pre-Conditioning Doses", Molecules and Cells, 33(1), pp.79~86 (2012), 한국분자세포생물학회
- 최정화, "Effects of Pre-conditioning dose on the Immune Kinetics and Cytokine Production in the Leukocytes Infiltrating GVHD Tissues after MHC-matched Transplantation", Immune Network, 11(1), pp.68~78 (2011), 대한면역학회
- Toubai, T., "Role of cytokines in the pathophysiology of acute graft-versus-host disease (GVHD): are erum", plasma cytokines potential biomarkers for diagnosis of acute GVHD following allogeneic hematopoietic cell transplantation (Allo- HCT)?, 2012, pp.7, 229~239
- Murai, M., "Peyer’s patch is the essential site in initiating murine acute and lethal graft-versus-host reaction", Nat. Immunol, 4, pp.154~160 (2003)
- Panoskaltsis-Mortari,. A, "In vivo imaging of graft-versus-host-disease in mice", Blood, 103, pp.3590~3598 (2004)
- Beilhack, A., "In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets", Blood, 106, pp.1113~1122 (2005)
- Koyama, M., "Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease", Nat. Med, 18, pp.135~142 (2011)
- Goker, H., "Acute graft-vs-host disease: pathobiology and management", Exp. Hematol, 29, pp.259~277 (2001)
- Visentainer, J. E., "Serum cytokine levels and acute graft-versus-host disease after HLA-identical hematopoietic stem cell transplantation", Exp. Hematol, 31, pp.1044~1050 (2003)
- Hill, G. R., "Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines", Blood, 90, pp.3204~3213 (1997)
- Nishimori, H., "Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17", Blood, 119, pp.285~295 (2012)
- Park, H, "A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17", Nat. Immunol, 6, pp.1133~1141 (2005)
- O'Connor, R. A, "Cutting edge: Th1 cells facilitate the entry of Th17 cells to the central nervous system during experimental autoimmune encephalomyelitis", J. Immunol, 181, pp.3750~3754 (2008)
- Zhao, F., "Blockade of osteopontin reduces alloreactive CD8＋ T cell-mediated graft-versus-host disease", Blood, 117, pp.1723~1733 (2011)
- Broady, R., "Cutaneous GVHD is associated with the expansion of tissue-localized Th1 and not Th17 cells", Blood, 116, pp.5748~5751 (2010)