Received May 2, 2007
Accepted on February 2, 2008

CLINICAL RESEARCH

Circulating Alloreactive T Cells Correlate with Graft Function in Longstanding Renal Transplant Recipients

Oriol Bestard ^*1, Peter Nickel ^*, Josep M. Cruzado , Constanze Schoenemann , Olaf Boenisch ^*, Anett Sefrin ^*, Josep M. Grinyó , Hans-Dieter Volk , and Petra Reinke ^*

*Department of Nephrology and Intensive Care, Charité Campus Virchow, HLA Laboratory, Institute for Medical Transfusion, and Institute of Medical Immunology, Charité Campus Mitte, Berlin, Germany; and Department of Nephrology, Hospital Univeristari de Bellvitge, Barcelona, Spain

¹ To whom correspondence should be addressed. E-mail: 35830obm{at}comb.es.

	Abstract

Monitoring for alloreactive memory T cells after organ transplantation may allow individualization of immunosuppression. Two pathways of T cell allorecognition have been implicated in chronic graft dysfunction: Direct (recipient T cells respond to donor peptides presented by donor antigen-presenting cells) and indirect (donor peptides are processed and presented by recipient antigen-presenting cells). Previous studies have assessed these alloresponses only during the first 2 yr after kidney transplantation, so this study correlated the presence of circulating donor-reactive memory/effector T cells, primed by both pathways, in 34 longstanding living-donor renal transplant recipients using the highly sensitive IFN- Elispot assay. Remarkably, 59% of patients had directly primed donor-reactive T cells, and their presence correlated directly with serum creatinine (P = 0.001) and inversely with estimated GFR (P = 0.042). Multivariate analysis revealed that hyporesponsiveness of direct, donor-specific T cells was the only variable that significantly correlated with graft function and that antidonor indirect alloreactivity was the only variable that significantly correlated with proteinuria. Interestingly, when both allorecognition pathways were considered together, patients with undetectable direct alloreactivity had better long-term graft function, independent of allosensitization by the indirect pathway. In conclusion, circulating donor-specific alloreactive T cells primed by both pathways are detectable long after transplantation and are associated with graft injury. Assessment of alloreactive memory/effector T cells might be helpful to tailor individual immunosuppression regimens for transplant recipients in the future.