A diffusible lymphokine produced by CD8+ T lymphocytes

Commentary

 * Summary of conclusions: The CD8+ subset of T cells produce a soluble substance that inhibits HIV replication


 * Finding 1: Phytohemagglutinin-stimulated CD8+ T cells mediate suppression of HIV-1 replication in autologous CD4+ T cells across a 0.45μm filter. (See Fig 2 and Table 1.)  A diffusible cytokine produced by the CD8+ cells suppresses HIV replication.
 * Confirmation: PMID 9060675: HIV-1-specific CD8+ cytotoxic T lymphocytes suppress HIV-1 replication across a 0.45μm filter when specifically stimulated by antigen (Figure 4)
 * Confirmation: PMID 1673156: Activated CD8+ T cells produce a soluble factor that inhibits HIV-1 replication, which is not IFN-beta, IFNgamma, or TNF-alpha


 * Finding 2: CD8+ T cell suppression of HIV-1 replication is more efficient if there is direct cell contact. (See Figure 3.)  Delivery of the cytokine is more efficient when there is cell contact.
 * Confirmation: PMID 9060675: HIV-1-specific CD8+ cytotoxic T lymphocytes are more effective at virus suppression when in direct contact with infected cells (Figure 6A)
 * Contradictory Study: PMID 9060675 finds: HIV-1-specific CD8+ cytotoxic T lymphocytes predominantly mediate antiviral activity through contact-mediated killing and not cytokine production (Figure 4)
 * Contradictory Study: PMID 8709196: HIV-1-specific CD8+ cytotoxic T lymphocytes efficiently kill infected cells at 100%, early in life cycle, in HLA-restricted fashion


 * The phenomenon of a cytokine inhibitor of HIV-1 produced by CD8+ T cells is generally accepted. However, most feel that this is a minor mechanism of antiviral activity, with numerous studies indicating that direct killing through cell contact is the major mechanism (references), although this is disputed by a few (references). For certain strains of HIV-1 that use CCR5 for entry, the beta chemokines MIP- 1a, MIP-1b, and RANTES have been shown to be CD8+ T cell-secreted cytokines that can block viral replication, but Levy et al have proposed that the major antiviral factor is not these cytokines because it also works against non-CCR5-using strains of HIV-1 (CXCR4-using) (references), which has been termed CAF (CD8 antiviral factor). Despite decades of studies of CAF mostly from the Levy group (references), and several candidates (references) and excluded cytokines (references), the identity of CAF remains obscure.