We propose that in HIV infection, while inflammatory cytokines and antigens drive more naïve and central memory CD8+ T cells into cell cycle, the resultant effector CD28- CD8+ T cells undergo fewer rounds of proliferation and fail to terminally differentiate [22], leading to enrichment for less well-differentiated transitional memory cells, with perhaps poorer killing capacity (Figure 6C). Here, CD8A is linked to HIV infectious disease.