Model of known factors that may contribute to impaired CD8 T-cell protection in HIV infection.

Contributory factors include (1) inefficient antigen presentation by HIV-infected cells because of nef-mediated down-modulation of MHC class I molecules or viral peptide escape mutation, (2) impaired or incomplete T-cell-receptor signaling because of CD3ζ and CD28 down-modulation, (3) up-regulation of NK inhibitory receptors, (4) lack of perforin for cytolysis, and (5) inefficient homing to lymphoid sites of infection. Many of these molecular events may not be unique to HIV infection but are integral to the regulated CD8 T-cell response to antigen.