In HIV disease progression, numerical decline and functional impairment of CD8+ T cells can be attributed to increased susceptibility to apoptosis from alterations in the cytokine milieu in lymphoid tissue, bystander effects from neighboring productively infected CD4+ T cells, and toxicity from the release of HIV-derived gp120 or Tat proteins, in addition to direct infection [13,14]. Here, CD4 is linked to infection.