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Allochimeric MHC I-Conditioned T Cells Attenuate Chronic Rejection in Rat Cardiac Model System | OMICS International | Abstract
ISSN: 2155-9899

Journal of Clinical & Cellular Immunology
Open Access

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Research Article

Allochimeric MHC I-Conditioned T Cells Attenuate Chronic Rejection in Rat Cardiac Model System

Thomas Skelton1,4, Andrea M Cordero2, Nicole J Nelles3, Malathesha Ganachari4, Jitinderpal Sidhu4, Neelam Tejpal1,4, Yongquan Gong1, Junping You1,4, Malgorzata Kloc1,4* and Rafik M. Ghobrial1,4*
1Department of Surgery, The Methodist Hospital, USA
2The Methodist DeBakey Heart & Vascular Center, USA
3Department of Pathology, The Methodist Hospital, Houston, TX, USA
4The Methodist Hospital Research Institute, Houston, TX, USA
Corresponding Authors : Rafik M. Ghobrial
The Methodist Hospital, Department of Surgery
6550 Fannin St., Houston, TX 77030, USA
Tel: 713.441.6875
Fax: 713.790.3755
E-mail: [email protected]
  Malgorzata Kloc
The Methodist Hospital, Department of Surgery
6550 Fannin St., Houston, TX 77030, USA
Tel: 713.441.6875
Fax: 713.790.3755
E-mail: [email protected]
Received June 07, 2011; Accepted July 23, 2011; Published July 27, 2011
Citation: Skelton T, Cordero AM, Nelles NJ, Ganachari M, Sidhu J, et al. (2011) Allochimeric MHC I-Conditioned T Cells Attenuate Chronic Rejection in Rat Cardiac Model System. J Clin Cell Immunol 2:108. doi:10.4172/2155-9899.1000108
Copyright: © 2011 Skelton T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

Background: We have shown previously that the mutated class I MHC molecules abrogate acute and chronic rejection and attenuate transplant vascular sclerosis (TVS) through the early changes (1-7 days post-transplantation) in T cell and dendritic cell molecular response. Here we studied a cohort of long-term (100 days) graft survival recipients for changes in T cell molecular response, and the role of regulatory T cells in the abrogation of chronic rejection in adoptive transfer experiments.
Methods: Heterotopic cardiac transplants were performed between donor Wistar Furth (WF) and ACI recipient rats. Controls received no treatment or 6 days therapeutic dose of cyclosporine (CsA 10mg/kg). The experimental group of primary ACI recipient received, peri-operatively, the allochimeric [[α]1h l/u]-RT1.Aa MHC I molecule (1mg/kg) in conjunction with the sub-therapeutic dose of CsA for 3 days. Splenic T cells were isolated from ACI recipient at 100 days post-transplantation and either assessed for changes in the expression of chosen protein markers or, in adoptive transfer experiments; they were injected into lightly irradiated secondary ACI recipients grafted with WF hearts. Secondary cardiac grafts were harvested at 100 days of post-transplantation for assessment of chronic rejection, neointimal index (NI) and apoptosis.
Results: Secondary cardiac grafts from recipients exposed to allochimeric MHC I-conditioned splenic total T cells or CD4+ T cells showed significantly reduced NI and apoptosis, and were selectively infiltrated with CD4+Foxp3+ (T regulatory, Treg) cells.
Conclusion: Adoptive transfer of allochimeric MHC I-conditioned T cells promotes development of Treg cells and attenuates chronic rejection in rat cardiac model system.

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