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The Role of Costimulatory Pathways in Transplant Tolerance

Mayuko Uehara1, Martina M McGrath1

  • 1Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA.

Clinics in Laboratory Medicine
|February 3, 2019
PubMed

Costimulation is a critical step in T-cell activation, and costimulatory blockade at the time of T cell activation leads to T-cell anergy and allograft tolerance in animal models of transplantation. CD28:B7 is the most important costimulatory pathway and the balance of signals between CD28 and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a central determinant of transplant outcome. Form a clinical standpoint, CTLA-4 Ig is the only approved agent for costimulation blockade in transplantation. Advantages and disadvantages of its use are discussed. Progress in developing novel agents to target other pathways, including the promising CD40:CD154 pathway, is also discussed.

Keywords:
CD154CD28CD40CTLA-4LFA-1Regulatory T cellT-cell costimulationTolerance

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