The effect of costimulatory and interleukin 2 receptor blockade on regulatory T
cells in renal transplantation.
Author(s): Bluestone JA, Liu W, Yabu JM, Laszik ZG, Putnam A, Belingheri M, Gross DM,
Townsend RM, Vincenti F.
Affiliation(s): Diabetes Center, Department of Medicine, University of California San Francisco,
CA, USA. jbluest@diabetes.ucsf.edu
Publication date & source: 2008, Am J Transplant. , 8(10):2086-96
Regulatory T cells (Treg) are critical regulators of immune tolerance. Both IL-2
and CD28-CD80/CD86 signaling are critical for CD4(+)CD25(+)FOXP3(+) Treg survival
in mice. Yet, both belatacept (a second-generation CTLA-4Ig) and basiliximab (an
anti-CD25 monoclonal antibody) are among the arsenal of current immunotherapies
being used in kidney transplant patients. In this study, we explored the direct
effect of basiliximab and belatacept on the Tregs in peripheral blood both in the
short term and long term and in kidney biopsies of patients with acute rejection.
We report that the combined belatacept/basiliximab therapy has no long-term
effect on circulating Tregs when compared to a calcineurin inhibitor
(CNI)-treated group. Moreover, belatacept-treated patients had a significantly
greater number of FOXP3(+) T cells in graft biopsies during acute rejection as
compared to CNI-treated patients. Finally, it appears that the basiliximab caused
a transient loss of both FOXP3(+) and FOXP3(-) CD25(+) T cells in the circulation
in both treatment groups raising important questions about the use of this
therapy in tolerance promoting therapeutic protocols.
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