Abstract
Acute graft-versus-host disease (GVHD) involves mainly skin, liver and intestines. Other organs such as heart, muscle and central nervous system are seldom affected, although their parenchymal cells also express alloantigens, such as MHC class I antigens. The mechanism of this selective involvement of distinct organs in acute GVHD is not well understood. We postulated that it might be related to the selective migration of activated alloreactive T cells. Indeed, T cell infiltration, revealed by examination of serial samples using flow cytometry and immunohistology, occurred early and continuously in the target organs such as the liver, but not in a non-target organ, the heart, in a murine acute GVHD model. Since T cell migration is largely controlled by the expression of chemokine and chemokine receptors, we investigated the chemokine spectrum in target/non-target organs of mice with acute GVHD. We found that in the spleen and liver MIP-1α, MIP-2 and Mig were the predominant chemokines expressed. In another target organ, the skin, MIP-1α, MIP-2, MCP-1 and MCP-3 were all highly expressed. In a non-target organ of acute GVHD, the heart, the predominant chemokines expressed were MCP-1 and MCP-3. This distinct pattern of chemokine expression in these organs may contribute to the preferential recruitment of inflammatory cells into the liver and skin, but not into the heart, in acute GVHD.
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References
Ferrara JL, Deeg HJ . Graft-versus-host disease New Engl J Med 1991 324: 667 674
Brok HP, Heidt PJ, van der Meide PH et al. Interferon-γ prevents graft-versus-host disease after allogeneic bone marrow transplantation in mice J Immunol 1993 151: 6451 6459
Dickinson AM, Sviland L, Hamilton PJ et al. Cytokine involvement in predicting clinical graft-versus-host disease in allogeneic bone marrow transplant recipients Bone Marrow Transplant 1994 13: 65 70
Allen RD, Staley TA, Sidman CL . Differential cytokine expression in acute and chronic murine graft-versus-host disease Eur J Immunol 1993 23: 333 337
Bouma GJ, van der Meer-prins E, van der Woude FJ et al. Relevance of pretransplant donor-specific T cell allorepertoire for human kidney graft survival Transplantation 1995 59: 969 976
Hu HZ, de Jonge N, Doornewaard H et al. Cytotoxic T lymphocytes infiltrating the human cardiac allograft show a restriction in T-cell receptor V beta gene usage: a study on serial biopsy and blood specimens J Heart Lung Transplant 1994 13: 1058 1071
Hu HZ, Li GL, Lim YK et al. Kinetics of interferon-γ secretion and its regulatory factors in the early phase of acute graft-versus-host disease Immunology 1999 98: 379 385
Hu HZ, New JY, Li B et al. Depletion of activated alloreactive T cells in prevention of acute graft-versus-host disease Transplant Proc 2000 32: 2456 2457
Li B, New JY, Yap EH et al. Blocking L-selectin and α4-integrin changes donor cell homing pattern and ameliorates murine acute graft versus host disease Eur J Immunol 2001 31: 617 624
Nikolic B, Lee S, Bronson RT et al. Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets J Clin Invest 2000 105: 1289 1298
Hakim F, Fowler DH, Shearer GM, Gress RE . Animal models of acute and chronic graft-versus-host disease Curr Protocols Immunol 1998 S27: 4.3.1 4.3.21
Murai M, Yoneyama H, Harada A et al. Active participation of CCR5+ CC8+ T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease J Clin Invest 1999 104: 49 57
Zlotnik A, Yoshie O . Chemokines: a new classification system and their role in immunity Immunity 2000 12: 121 127
Baggiolini M . Chemokines and leukocyte traffic Nature 1998 392: 565 568
Rollins BJ . Chemokines Blood 1997 90: 909 928
Serody JS, Burkett SE, Panoskaltsis-Mortari A et al. T-lymphocyte production of macrophage inflammatory protein-1α is critical to the recruitment of CD8+ T cells to the liver, lung and spleen during graft-versus-host disease Blood 2000 96: 2973 2980
Bonecchi R, Bianchi G, Bordignon PP et al. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s J Exp Med 1998 187: 129 134
Sallusto F, Lanzavecchia A, Mackay CR . Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses Immunol Today 1998 19: 568 574
Nelson PJ, Krensky AM . Chemokines, chemokine receptors and allograft rejection Immunity 2001 14: 377 386
Zingoni A, Soto H, Hedrick JA et al. The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells J Immunol 1998 161: 547 551
Lu Y, Sakamaki S, Kuroda H et al. Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603 Blood 2001 97: 1123 1130
Wolpe SD, Sherry B, Juers D et al. Identification and characterization of macrophage inflammatory protein 2 Proc Natl Acad Sci USA 1989 86: 612 616
Mercer-Jones MA, Shrotri MS, Heinzelmann M et al. Regulation of early peritoneal neutrophil migration by macrophage inflammatory protein-2 and mast cells in experimental peritonitis J Leukoc Biol 1999 65: 249 255
Ebert LM, McColl SR . Coregulation of CXC chemokine receptor and CD4 expression on T lymphocytes during allogeneic activation J Immunol 2001 166: 4870 4878
Koga S, Auerbach MB, Engeman TM et al. T cell infiltration into class II MHC-disparate allografts and acute rejection is dependent on the IFN-γ-induced chemokine Mig J Immunol 1999 163: 4878 4885
Grone HJ, Weber C, Weber KS et al. Met-RANTES reduces vascular and tubular damage during acute renal transplant rejection: Blocking monocyte arrest and recruitment FASEB J 1999 13: 1371 1383
Hancock WW, Lu B, Gao W et al. Requirement of the chemokine receptor CXCR3 for acute allograft rejection J Exp Med 2000 192: 1515 1520
Acknowledgements
This work was supported by grants 30030, NMRC/0348/1999, NMRC/0327/1999 (HZH) from the National Medical Research Council, Singapore, and a grant from Leukemia Research Foundation (HZH).
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New, J., Li, B., Koh, W. et al. T cell infiltration and chemokine expression: relevance to the disease localization in murine graft-versus-host disease. Bone Marrow Transplant 29, 979–986 (2002). https://doi.org/10.1038/sj.bmt.1703563
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DOI: https://doi.org/10.1038/sj.bmt.1703563
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