Oligoclonality of CD8+ T cells in health and disease: aging, infection, or immune regulation?

Oligoclonality of the CD8+ T cell subset is a common and characteristic feature of the normal human peripheral T cell repertoire. These clonally expanded populations are predominantly found in a CD57+ or CD28- CD8+ T cell subset. While CD8 oligoclonality is somewhat more common in the older age group, it is also very prevalent in young to middle-aged adults. Recent experiments have also demonstrated that the clonally expanded populations may actually occur in two distinct subpopulations of CD8+ CD28- cells, distinguished by the expression of the CD57 surface marker. A major difficulty with studies involving CD8+ CD28- CD57+ T cells is their relative lack of proliferative capacity. We have recently investigated the possibility that this phenotype may be due to a state of "replicative senescence" in some cases. In this regard, we have demonstrated that the telomere lengths of CD8+ CD28- T cells are generally shorter than that of their CD8+ CD28+ counterparts, consistent with a distinct replicative history for the CD8+ CD28- population. Additional studies of the normal biology of clonally expanded CD8+ T cells are likely to yield important insights into immune function in health and disease.