Unusual CD4⁺CD28⁻ T Cells and Their Pathogenic Role in Chronic Inflammatory Disorders

CD28 is a primary co-stimulatory receptor that is essential for successful T cell activation, proliferation, and survival. While ubiquitously expressed on naive T cells, the level of CD28 expression on memory T cells is largely dependent on the T-cell differentiation stage in humans. Expansion of circulating T cells lacking CD28 was originally considered a hallmark of age-associated immunological changes in humans, with a progressive loss of CD28 following replicative senescence with advancing age. However, an increasing body of evidence has revealed that there is a significant age-inappropriate expansion of CD4⁺CD28⁻ T cells in patients with a variety of chronic inflammatory diseases, suggesting that these cells play a role in their pathogenesis. In fact, expanded CD4⁺CD28⁻ T cells can produce large amounts of proinflammatory cytokines such as IFN-γ and TNF-α and also have cytotoxic potential, which may cause tissue damage and development of pathogenesis in many inflammatory disorders. Here we review the characteristics of CD4⁺CD28⁻ T cells as well as the recent advances highlighting the contribution of these cells to several disease conditions.

Analysis of T lymphocyte subsets in patients with primary biliary cirrhosis / 中华风湿病学杂志

Objective To investigate the significance and characteristics of T lymphocyte subsets and co-stimulatory CD28 in peripheral blood of patients with primary biliary cirrhosis. Methods Tri-colour flow-cytometry was used to detect the levels of T lymphocyte subsets in peripheral blood in 98 patients with primary biliary cirrhosis and 30 age and gender matched healthy controls. Results Compared to control group the percentage of CD4+ T increased and CD8+ T lymphocyte decreased in the PBC group. The CD4+/CD8+ ratio in the PBC group was higher than that in the control group (P<0.05). And the percentage of CD4+CD28- T cells and CD8+CD28- T cells increased, too (P<0.05). Conclusion There are immunological abnormalities in PBC and the expression of co-stimulator CD28 is significantly decreased. CD8+CD28-T lymphocytes may have immune regulatory effect in PBC.