CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. T cell stimulation through CD28 in addition to the T-cell receptor (TCR) can provide a potent signal for the production of various interleukins (IL-6 in particular). CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins. When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen-presenting cells (APCs). The CD86 expression on antigen-presenting cells is constitutive (expression is independent of environmental factors). CD28 is the only B7 receptor constitutively expressed on naive T cells. Association of the TCR of a naive T cell with MHC:antigen complex without CD28:B7 interaction results in a T cell that is anergic. Furthermore, CD28 was also identified on bone marrow stromal cells, plasma cells, neutrophils and eosinophils, but the functional importance of CD28 on these cells is not completely understood. It is generally reported, that CD28 is expressed on 50% of CD8+ T cells and more than 80% CD4+ T cells in human, but during the course of activation some T cells lose this molecule. Some antigen-experienced T cells lose CD28 and subsequently can be re-activated without CD28 engagement. These CD28− T cells have generally been characterized as antigen specific and terminally differentiated, and are often described as being memory T cells (TMs). In addition, the level of positive CD28 decreases with age. As a homodimer of two chains with Ig domains binds B7 molecules on APCs and it can promotes T cells proliferation and differentiation, stimulates production of growth factors and induces the expression of anti-apoptotic proteins. According to several studies, after birth, all human cells express CD28. But in adult, 20-30% of CD8+ T cells lose the ability of CD28 expression, whereas in the elderly (+80 years) up to 50-60% of CD8+ cells lose the ability of CD28 expression. But these statements only suggest that loss of CD28 expression marks functional differentiation to cytotoxic memory cells within clonal expansions. In general, CD28 is a primary costimulatory molecule for T cell activation. But effective co-stimulation is essential only for some T cell activation. In this case, in the absence of co-stimulatory signals, the interaction of dendritic and T cells leads to T cell anergy. The importance of the costimulatory pathway is underlined by the fact that antagonists of co-stimulatory molecules disrupt the immune responses both