CD28

CD28 (Cluster of Differentiation 28) is a protein expressed on T cells that provides essential co-stimulatory signals required for T cell activation and survival. When T cells are stimulated through CD28 in conjunction with the T-cell receptor (TCR), it enhances the production of various interleukins, particularly IL-6. CD28 serves as a receptor for CD80 (B7.1) and CD86 (B7.2), proteins found on antigen-presenting cells (APCs).

CD28 is the only B7 receptor consistently expressed on naive T cells. In the absence of CD28:B7 interaction, a naive T cell's TCR engagement with an MHC:antigen complex leads to anergy. CD28 is also expressed on bone marrow stromal cells, plasma cells, neutrophils, and eosinophils, although its function in these cells is not fully understood.

Typically, CD28 is expressed on about 50% of CD8+ T cells and more than 80% of CD4+ T cells in humans. However, some T cells lose CD28 expression during activation, particularly antigen-experienced T cells, which can be re-activated independently of CD28. These CD28⁻ T cells are often antigen-specific, terminally differentiated, and categorized as memory T cells (TMs). The proportion of CD28⁻ T cells increases with age.

As a homodimer with Ig domains, CD28 binds B7 molecules on APCs, promoting T cell proliferation, differentiation, growth factor production, and the expression of anti-apoptotic proteins. While CD28 is crucial for T cell activation, particularly in initial immune responses, some antigen-experienced T cells can function without it, marking their differentiation into cytotoxic memory cells.