CD28 and CD57 define four populations with distinct phenotypic properties within human CD8+ T cells

After repeated antigen exposure, both memory and terminally differentiated cells can be generated within CD8(+) T cells. Although, during their differentiation, activated CD8(+) T cells may first lose CD28, and CD28(-) cells may eventually express CD57 as a subsequent step, a population of CD28(+)CD57(+)(DP) CD8(+) T cells can be identified in the peripheral blood. How this population is distinct from CD28(-)CD57(-)(DN) CD8(+) T cells, and from the better characterized non-activated/early-activated CD28(+)CD57(-) and senescent-like CD28(-)CD57(+) CD8(+) T cell subsets is currently unknown. Here, RNA expression of the four CD8(+) T cell subsets isolated from human PBMCs was analyzed using microarrays. DN cells were more similar to early highly differentiated cells, with decreased TNF and IFN-gamma production, impaired DNA damage response and apoptosis. Conversely, increased apoptosis and expression of cytokines, co-inhibitory, and chemokine receptors were found in DP cells. Higher levels of DP CD8(+) T cells were observed 7 days after Hepatitis B vaccination, and decreased levels of DP cells were found in rheumatoid arthritis patients. More DP and DN CD8(+) T cells were present in the bone marrow, in comparison with PBMCs. In summary, our results indicate that DP and DN cells are distinct CD8(+) T cell subsets displaying defined properties.