Monokine induced by interferon-gamma (MIG/CXCL9) is derived from both donor and recipient sources during rejection of class II major histocompatibility complex disparate skin allografts.

Chemokines, including monokine induced by interferon-gamma (Mig/CXCL9), are produced both in allografts and during the direct T-cell infiltration that mediates graft rejection. Neither the specific production nor contribution of allograft donor versus recipient Mig in allograft rejection is currently known. C57BL/6 mice with a targeted deletion in the Mig gene were used as both skin allograft donors and recipients in a class II major histocompatibility complex-mismatched graft model to test the requirement for donor- versus recipient-derived Mig for acute rejection. B6.Mig(-/-) allografts had a 10-day prolonged survival in B6.H-2(bm12) recipients when compared with wild-type C57BL/6 allograft donors, and B6.H-2(bm12) skin allografts had a 5-day prolonged survival in B6.Mig(-/-) versus wild-type recipients. Transplantation of B6.Mig(-/-) skin grafts onto B6.H-2(bm12).Mig(-/-) recipients resulted in further prolonged allograft survival with more than 30% of the grafts surviving longer than 60 days. Prolonged allograft survival was also associated with delayed cellular infiltration into grafts but not with altered T-cell proliferative responses to donor stimulators. Immunohistochemical staining of allograft sections indicated that Mig is produced by both donor- and recipient-derived sources, but Mig from each of these sources appeared in different areas of the allograft tissue. These results therefore demonstrate the synergy of donor- and recipient-derived Mig in promoting T-cell infiltration into allografts.

[1]  R. Gill,et al.  LFA‐1 (CD11a) as a Therapeutic Target , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[2]  M. Fishbein,et al.  Chemokine Monokine Induced by IFN-γ/CXC Chemokine Ligand 9 Stimulates T Lymphocyte Proliferation and Effector Cytokine Production1 , 2004, The Journal of Immunology.

[3]  W. Hancock,et al.  Chemokines and their receptors as markers of allograft rejection and targets for immunosuppression. , 2003, Current opinion in immunology.

[4]  R. Fairchild,et al.  Absence of Allograft ICAM-1 Attenuates Alloantigen-Specific T Cell Priming, But Not Primed T Cell Trafficking into the Graft, to Mediate Acute Rejection1 , 2003, The Journal of Immunology.

[5]  P. McCarthy,et al.  Chemokine and chemokine receptor gene expression indicates acute rejection of human cardiac transplants1 , 2003, Transplantation.

[6]  A. Novick,et al.  Chronic antagonism of Mig inhibits cellular infiltration and promotes survival of class II MHC disparate skin allografts , 2002, Transplantation.

[7]  O. Lantz,et al.  Cross-primed CD8+ T cells mediate graft rejection via a distinct effector pathway , 2002, Nature Immunology.

[8]  A. Iwasaki,et al.  The CXC Chemokine Murine Monokine Induced by IFN-γ (CXC Chemokine Ligand 9) Is Made by APCs, Targets Lymphocytes Including Activated B Cells, and Supports Antibody Responses to a Bacterial Pathogen In Vivo , 2002, The Journal of Immunology.

[9]  H. Auchincloss,et al.  The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection. , 2002, Diabetes.

[10]  Myoung Soo Kim,et al.  Evidence that the ratio of donor kidney weight to recipient body weight, donor age, and episodes of acute rejection correlate independently with live-donor graft function1,2 , 2002, Transplantation.

[11]  G. McMahon,et al.  Expression of the Chemokine Receptor CXCR3 and Its Ligand IP-10 During Human Cardiac Allograft Rejection , 2001 .

[12]  W. Hancock,et al.  Beneficial effects of targeting CCR5 in allograft recipients. , 2001, Transplantation.

[13]  M. Burdick,et al.  Monokine Induced by IFN-γ Is a Dominant Factor Directing T Cells into Murine Cardiac Allografts During Acute Rejection1 , 2001, The Journal of Immunology.

[14]  W. Hancock,et al.  Requirement of the Chemokine Receptor CXCR3 for Acute Allograft Rejection , 2000, The Journal of experimental medicine.

[15]  C. Mackay,et al.  T-cell function and migration. Two sides of the same coin. , 2000, The New England journal of medicine.

[16]  C. Tannenbaum,et al.  Intraallograft Chemokine RNA and Protein During Rejection of MHC-Matched/Multiple Minor Histocompatibility-Disparate Skin Grafts1 , 2000, The Journal of Immunology.

[17]  A. Novick,et al.  T cell infiltration into class II MHC-disparate allografts and acute rejection is dependent on the IFN-gamma-induced chemokine Mig. , 1999, Journal of immunology.

[18]  J. Farber.  Mig and IP‐10: CXC chemokines that target lymphocytes , 1997, Journal of leukocyte biology.

[19]  Simon A. Jones,et al.  Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes , 1996, The Journal of experimental medicine.

[20]  A. Novick,et al.  Induction of chemokine gene expression during allogeneic skin graft rejection. , 1996, Transplantation.

[21]  L. Koniaris,et al.  Human Mig chemokine: biochemical and functional characterization , 1995, The Journal of experimental medicine.

[22]  S. Fuggle,et al.  VARIATION IN EXPRESSION OF ENDOTHELIAL ADHESION MOLECULES IN PRETRANSPLANT AND TRANSPLANTED KIDNEYS‐CORRELATION WITH INTRAGRAFT EVENTS , 1993, Transplantation.

[23]  C. Orosz,et al.  Importance of endothelial VCAM-1 for inflammatory leukocytic infiltration in vivo. , 1992, Journal of immunology.

[24]  M. Isobe,et al.  Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. , 1992, Science.

[25]  B. Hall,et al.  Cells mediating allograft rejection. , 1991, Immunological reviews.

[26]  H. Winn,et al.  The vascular bed as the primary target in the destruction of skin grafts by antiserum. II. Loss of sensitivity to antiserum in long-term xenografts of skin , 1981, The Journal of experimental medicine.

[27]  R. Colvin,et al.  The vascular bed as the primary target in the destruction of skin grafts by antiserum. I. Resistance of freshly placed xenografts of skin to antiserum , 1981, The Journal of experimental medicine.

[28]  M. Mihm,et al.  The microvasculature is the critical target of the immune response in vascularized skin allograft rejection. , 1980, Journal of Investigative Dermatology.

[29]  M. Mihm,et al.  Rejection of first-set skin allografts in man. the microvasculature is the critical target of the immune response , 1979, The Journal of experimental medicine.

[30]  P. Medawar,et al.  The Technique of Free Skin Grafting in Mammals , 1951 .

[31]  A. Novick,et al.  Antibody-Mediated Rejection of Cardiac Allografts in CCR5-Deficient Recipients , 2007 .

[32]  三浦 正義.  Monokine induced by IFN-γ is a dominant factor directing T cells into murine cardiac allografts during acute rejection , 2003 .

[33]  A. Singer,et al.  Cellular basis of skin allograft rejection: an in vivo model of immune-mediated tissue destruction. , 1992, Annual review of immunology.