A direct comparison of rejection by CD8 and CD4 T cells in a transgenic model of allotransplantation

• Authors: P.M. Porrett , IV M.K. Lee , M.M. Lian , J. Wang , A.J. Caton , S. Deng , J.E. Markmann , D.J. Moore
• Languages of publication: EN

Abstracts

EN

Introduction: The relative contributions of CD4+ and CD8+ T cells to transplant rejection remains unknown. The authors integrated a previous model of CD4-mediated graft rejection with a complementary model of CD8-mediated rejection to directly compare the function of graft-reactive CD4+ and CD8+ lymphocytes in vivo in a model where rejection requires transgenic T cells. These studies allow direct comparison of CD4 and CD8 T cell responses to the same antigen without the confounding effects of T cell depletion or homeostatic proliferation. Materials and Methods: Clone 4 and TS1 mice possess MHC class I- and II-restricted CD8+ and CD4+ T cells, respectively, which express transgenic T cell receptors that recognize the influenza hemagglutinin antigen (HA). We compared the in vivo response of CFSE-labeled, HA-specific transgenic CD8+ and CD4+ T cells after adoptive transfer into syngeneic BALB/c mice grafted with HA-expressing skin. Results: As in the authors' CD4+ model, HA104 skin was consistently rejected by both Clone 4 mice (n=9, MST: 14.2) and by 5x105 Clone 4 lymphocytes transferred to naive BALB/c hosts that do not otherwise reject HA+ grafts. Rejection correlated with extensive proliferation of either graft-reactive T cell subset in the draining lymph nodes, and antigen-specific CD4+ and CD8+ cells acquired effector function and proliferated with similar kinetics.Conclusions: These data extend the authors' unique transgenic transplantation model to the investigation of CD8 T cell function. The initial results confirm fundamental functional similarity between the CD4 and CD8 T cell subsets and provide insight into the considerable redundancy underlying T cell mechanisms mediating allograft rejection.

Keywords

EN

CD4 CELL; CD8 CELL; DIFFERENTIATION; PROLIFERATION; REJECTION; TRANSPLANTATION

Discipline

• IMMUNOLOGY: IMMUNOLOGY

• Publisher: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
• Journal: Archivum Immunologiae et Therapiae Experimentalis
• Year: 2008
• Volume: 56
• Issue: 3
• Pages: 192-200

Contributors

author

P.M. Porrett

author

IV M.K. Lee

author

M.M. Lian

author

J. Wang

author

A.J. Caton

author

S. Deng

author

J.E. Markmann

author

D.J. Moore

• Document Type: ARTICLE
• Publication order reference: Daniel J. Moore, Harrison Department of Surgical Research, Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104, USA