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T-cell exhaustion in allograft rejection and tolerance

Thorp, Edward B.a; Stehlik, Christianb; Ansari, M. Javeedc

Current Opinion in Organ Transplantation: February 2015 - Volume 20 - Issue 1 - p 37–42
doi: 10.1097/MOT.0000000000000153
MECHANISMS OF REJECTION: Edited by Jerzy W. Kupiec-Weglinski

Purpose of review The role of T-cell exhaustion in the failure of clearance of viral infections and tumors is well established. There are several ongoing trials to reverse T-cell exhaustion for treatment of chronic viral infections and tumors. The mechanisms leading to T-cell exhaustion and its role in transplantation, however, are only beginning to be appreciated and are the focus of the present review.

Recent findings Exhausted T cells exhibit a distinct molecular profile reflecting combinatorial mechanisms involving the interaction of multiple transcription factors important in control of cell metabolism, acquisition of effector function and memory capacity. Change of microenvironmental cues and limiting leukocyte recruitment can modulate T-cell exhaustion. Impaired leukocyte recruitment induces T-cell exhaustion and prevents allograft rejection.

Summary Preventing or reversing T-cell exhaustion may lead to prevention of transplant tolerance or triggering of rejection; therefore, caution should be exercised in the use of agents blocking inhibitory receptors for the treatment of chronic viral infections or tumors in transplant recipients. Further definition of the role of T-cell exhaustion in clinical transplantation and an understanding of the mechanisms of induction of T-cell exhaustion are needed to develop strategies for preventing allograft rejection and induction of tolerance.

aDepartment of Pathology

bDivision of Rheumatology

cDivisions of Nephrology and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, USA

Correspondence to Dr M. Javeed Ansari, MD, MRCP, Assistant Professor of Medicine, Divisions of Nephrology and Organ Transplantation, Northwestern University Feinberg School of Medicine, 300 East Superior St. Tarry Bldg, Suite 11-723, Chicago, IL 60611, USA. Tel: +1 312 503 2677; fax: +1 312 503 3366; e-mail:

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