CD28nullCD4⁺ T cells: an effector memory T cell population in patients with rheumatoid arthritis

Background

CD4⁺ T cells lacking the costimulatory molecule CD28 have been described in both elderly individuals and in several chronic inflammatory disorders, one being rheumatoid arthritis (RA).

Objective

We characterized such CD28nullCD4⁺ T cells from RA patients in order to identify surface markers correlating with function.

Methods

Peripheral blood mononuclear cells were analyzed for surface marker expression by flow cytometry and in vitro cultures were set up for functional studies.

Results

One-third of the RA patients had a persistent and expanded CD28null population, which comprised up to half of the CD4⁺ T cells in peripheral blood. Functionally, CD28nullCD4⁺ T cells were potent effector memory cells with regard to their proliferation and cytokine secretion profiles. This functional capacity correlated with a hitherto unpublished surface phenotype, the cells being uniformly CCR7-negative and CD43high. In addition, we re-evaluated previously suggested cell surface markers, and found CD57 and CD11b expressed on the majority of these NKT-like CD4⁺ T cells. When combining phenotypic and functional analyses of subpopulations of the CD28nullCD4⁺ T cells a new terminally differentiated T cell population was identified.

Conclusion

We believe that in the balanced immune system of healthy individuals, CD28nullCD4⁺ T cells are under homeostatic control, whereas in an unbalanced immune system such as in autoimmune disease CD28nullCD4⁺ T cells are allowed to expand and have the capacity to enhance ongoing inflammatory reactions.