CD28 extinction in human T cells: altered functions and the program of T-cell senescence

Authors

  • Abbe N. Vallejo

    Corresponding author
    1. Departments of Pediatrics and Immunology, University of Pittsburgh School of Medicine, Division of Rheumatology, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
    Search for more papers by this author

* Dr Abbe N. Vallejo
University of Pittsburgh School of Medicine
Children's Hospital of Pittsburgh
Rangos Research Center Suite 2122
3705 Fifth Avenue
Pittsburgh, PA 15213
USA
E-mail: abbe.vallejo@chp.edu

Abstract

Summary:  The loss of CD28 expression on T cells is the most consistent biological indicator of aging in the human immune system, and the frequency of CD28null T cells is a key predictor of immune incompetence in the elderly. There is also mounting evidence for the high frequency of these unusual T cells among patients with inflammatory syndromes or with chronic infections disproportionate with their age. In these pathological states, CD28null T cells likely represent prematurely senescent lymphocytes due to persistent immune activation. Unlike the situation in CD28 gene knockout mice that have anergic CD280/0 T cells, human CD28null T cells are functionally active, long-lived, oligoclonal lymphocytes that lack or have limited proliferative capacity. Results of replicative senescence studies show that CD28null T cells are derived from CD28+ precursors that have undergone repeated stimulation, indicating that CD28 silencing underlies the program of T-cell aging. Dissection of the machinery regulating CD28 expression is paving the way in elucidating the molecular events leading to immune senescence as well as providing clues into the functional rejuvenation of senescent T cells.

Ancillary