NDLI: Effect of triple costimulation blockade on islet allograft survival in sensitized mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Diab, R. Iwata, T. Corbascio, M. Tibell, A. Ekberg, H. Holgersson, J. Kumagai-Braesch, M.
Description	Country affiliation: Sweden Author Affiliation: Diab R ( Department of Laboratory Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet, Stockholm, Sweden.)
Abstract	BACKGROUND: Islet allograft rejection in sensitized recipients is difficult to control by costimulation blockade using anti-CD154 and cytotoxic T-lymphocyte antigen-4 immunoglobulin (CTLA4Ig). Because leukocyte function antigen (LFA) 1 is highly expressed on memory T cells, adding an LFA-1 blockade may inhibit memory T-cell activities. We examined the effects on islet allograft survival of triple costimulation blockade in presensitized recipient mice. METHODS: C57BL/6 mice were sensitized by transplantation under the kidney capsule or intraperitoneal injection of Balb/c islets. Four weeks after transplantation, sensitization was confirmed by flow-cytometric detection of alloreactive antibodies. Diabetes was induced by a single intravenous injection of streptozotocin. Recipients were transplanted with 200 Balb/c islets under the right kidney capsule. Graft function was assessed by daily blood glucose and body weight records. Transplanted animals were divided into 3 treatment groups: group 1, control antibody; group 2, anti-CD154 and CTLA-4 Ig double therapy; group 3, anti-CD154, CTLA4Ig, and anti-LFA-1 triple therapy. Injections were administered every second day from day -2 to day 8. RESULTS: Naïve mice rejected islet allografts between days 7 and 29 (mean 16 +/- 6 d; n = 5), sensitized mice in group 1 between days 0 and 14 (mean 7 +/- 5 d; n = 8), in group 2 between days 4 and 16 (mean 8 +/- 4 d; n = 7), and in group 3 between days 4 and 26 (mean 11 +/- 7 d; n = 10). CONCLUSION: Triple costimulation blockade with anti-CD154, CTLA4Ig, and anti-LFA-1 was not sufficient to improve islet allograft survival in sensitized recipients.
File Format	HTM / HTML
ISSN	00411345
e-ISSN	18732623
DOI	10.1016/j.transproceed.2010.05.084
Journal	Transplantation Proceedings
Issue Number	6
Volume Number	42
Language	English
Publisher	Elsevier
Publisher Date	2010-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Transplantation__semicolon__medicine Diabetes Mellitus, Experimental Surgery Graft Survival Physiology Islets Of Langerhans Transplantation Transplantation, Homologous Animals Antigens, Cd Immunology Blood Glucose Metabolism Ctla-4 Antigen Blood Graft Rejection Immunoglobulin G Pathology Mice Mice, Inbred Balb C Mice, Inbred C57bl Reoperation Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Transplantation Surgery

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Effect of Triple Costimulation Blockade on Islet Allograft Survival in Sensitized Mice

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