HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abdi, R. Articles by Sayegh, M. H. Search for Related Content PubMed PubMed Citation Articles by Abdi, R. Articles by Sayegh, M. H. Social Bookmarking                What's this?

The Role of CC Chemokine Receptor 5 (CCR5) in Islet Allograft Rejection

¹ Laboratory of Immunogenetics and Transplantation, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
² Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
³ Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
⁴ Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4⁺ T helper 1 (Th1) cells. We sought to determine the role of CCR5 in islet allograft rejection in a streptozotocin-induced diabetic mouse model. BALB/c islet allografts transplanted into CCR5^-/- (C57BL/6) recipients survived significantly longer (mean survival time, 38 ± 8 days) compared with those transplanted into wild-type control mice (10 ± 2 days; P < 0.0001). Twenty percent of islet allografts in CCR5^-/- animals without other treatment survived >90 days. In CCR5^-/- mice, intragraft mRNA expression of interleukin-4 and -5 was increased, whereas that of interferon- was decreased, corresponding to a Th2 pattern of T-cell activation in the target tissues compared with a Th1 pattern observed in controls. A similar Th2 response pattern was also observed in the periphery (splenocytes responding to donor cells) by enzyme-linked immunosorbent spot assay. We conclude that CCR5 plays an important role in orchestrating the Th1 immune response leading to islet allograft rejection. Targeting this chemokine receptor, therefore, may provide a clinically useful strategy to prevent islet allograft rejection.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				T. Nozaki, H. Amano, A. Bickerstaff, C. G. Orosz, A. C. Novick, K. Tanabe, and R. L. Fairchild Antibody-Mediated Rejection of Cardiac Allografts in CCR5-Deficient Recipients J. Immunol., October 15, 2007; 179(8): 5238 - 5245. [Abstract] [Full Text] [PDF]

				P. Fiorina, M. Jurewicz, K. Tanaka, N. Behazin, A. Augello, A. Vergani, U. Von Adrian, N. R. Smith, M. H. Sayegh, and R. Abdi Characterization of Donor Dendritic Cells and Enhancement of Dendritic Cell Efflux With cc-Chemokine Ligand 21: A Novel Strategy to Prolong Islet Allograft Survival Diabetes, April 1, 2007; 56(4): 912 - 920. [Abstract] [Full Text] [PDF]

				C. Meagher, G. Arreaza, A. Peters, C. A. Strathdee, P. A. Gilbert, Q.-S. Mi, P. Santamaria, G. A. Dekaban, and T. L. Delovitch CCL4 Protects From Type 1 Diabetes by Altering Islet {beta}-Cell-Targeted Inflammatory Responses Diabetes, March 1, 2007; 56(3): 809 - 817. [Abstract] [Full Text] [PDF]

				M. Kallikourdis, K. G. Andersen, K. A. Welch, and A. G. Betz Alloantigen-enhanced accumulation of CCR5+ 'effector' regulatory T cells in the gravid uterus PNAS, January 9, 2007; 104(2): 594 - 599. [Abstract] [Full Text] [PDF]

				C. A. Bursill, J. L. Cash, K. M. Channon, and D. R. Greaves Membrane-Bound CC Chemokine Inhibitor 35K Provides Localized Inhibition of CC Chemokine Activity In Vitro and In Vivo J. Immunol., October 15, 2006; 177(8): 5567 - 5573. [Abstract] [Full Text] [PDF]

				H. Amano, A. Bickerstaff, C. G. Orosz, A. C. Novick, H. Toma, and R. L. Fairchild Absence of Recipient CCR5 Promotes Early and Increased Allospecific Antibody Responses to Cardiac Allografts J. Immunol., May 15, 2005; 174(10): 6499 - 6508. [Abstract] [Full Text] [PDF]

				B. Schroppel, N. Zhang, P. Chen, W. Zang, D. Chen, K. L. Hudkins, W. A. Kuziel, R. Sung, J. S. Bromberg, and B. Murphy Differential Expression of Chemokines and Chemokine Receptors in Murine Islet Allografts: The Role of CCR2 and CCR5 Signaling Pathways J. Am. Soc. Nephrol., July 1, 2004; 15(7): 1853 - 1861. [Abstract] [Full Text] [PDF]

				R. Abdi, T. K. Means, T. Ito, R. N. Smith, N. Najafian, M. Jurewicz, V. Tchipachvili, I. Charo, H. Auchincloss Jr., M. H. Sayegh, et al. Differential Role of CCR2 in Islet and Heart Allograft Rejection: Tissue Specificity of Chemokine/Chemokine Receptor Function In Vivo J. Immunol., January 15, 2004; 172(2): 767 - 775. [Abstract] [Full Text] [PDF]

				I. Lee, L. Wang, A. D. Wells, Q. Ye, R. Han, M. E. Dorf, W. A. Kuziel, B. J. Rollins, L. Chen, and W. W. Hancock Blocking the Monocyte Chemoattractant Protein-1/CCR2 Chemokine Pathway Induces Permanent Survival of Islet Allografts through a Programmed Death-1 Ligand-1-Dependent Mechanism J. Immunol., December 15, 2003; 171(12): 6929 - 6935. [Abstract] [Full Text] [PDF]