CD28 Negative T Cells: Is Their Loss Our Gain?

• Type of Material: Article
• Authors: Danny Mou, Emory University; Jaclyn Espinosa, Emory University; Denise Lo, Emory University; Allan Kirk, Emory University
• Language: English
• Date: 2014-11-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.
• Final Published Version (URL): http://dx.doi.org/10.1111/ajt.12937
• Title of Journal or Parent Work: American Journal of Transplantation
• ISSN: 1600-6135
• Volume: 14
• Issue: 11
• Start Page: 2460
• End Page: 2466
• Keywords: immune modulation; science; immunosuppression; RENAL-TRANSPLANTATION; Surgery; SUPPRESSOR-CELLS; costimulation; MEMORY; clinical research; DISEASE; TRANSPLANT RECIPIENTS; immunobiology; Basic (laboratory) research; Science & Technology; Life Sciences & Biomedicine; organ transplantation in general; Transplantation; practice; CD8(+)CD28(-); LYMPHOCYTES; CD8(+) CD28(-); T cell biology; RISK-FACTORS; HOMEOSTATIC REPOPULATION
• Research Categories: Biology, Cell; Health Sciences, Immunology; Health Sciences, Medicine and Surgery

Abstract

CD28 is a primary costimulation molecule for T cell activation. However, during the course of activation some T cells lose this molecule and assume a CD28-independent existence. These CD28- T cells are generally antigen-experienced and highly differentiated. CD28- T cells are functionally heterogeneous. Their characteristics vary largely on the context in which they are found and range from having enhanced cytotoxic abilities to promoting immune regulation. Thus, CD28 loss appears to be more of a marker for advanced differentiation regardless of the cytotoxic or regulatory function being conducted by the T cell. CD28- T cells are now being recognized as playing significant roles in several human diseases. Various functional CD28- populations have been characterized in inflammatory conditions, infections and cancers. Of note, the recent introduction of costimulation blockade-based therapies, particularly those that inhibit CD28-B7 interactions, has made CD28 loss particularly relevant for solid organ transplantation. Certain CD28- T cell populations seem to promote allograft tolerance whereas others contribute to alloreactivity and costimulation blockade resistant rejection. Elucidating the interplay between these populations and characterizing the determinants of their ultimate function may have relevance for clinical risk stratification and personal determination of optimal posttransplant immune management. The authors provide an overview of the circumstances leading to loss of the critical T cell costimulatory molecule CD28, and they discuss the transplant-relevant consequences of this sign of progressive T cell maturation.