Double-negative T cells during HIV/SIV infections: potential pinch hitters in the T-cell lineup

This review summarizes the role of CD3+CD4-CD8- double-negative T cells, which have both regulatory and helper T-cell functions and may have the potential to compensate for the reduced levels of CD4 T cells during SIV/HIV infection.

Double-negative T cells have been characterized in several human diseases and in murine models of autoimmunity and transplantation, where they exhibit both immunoregulatory and helper T-cell-like function. During the natural nonpathogenic SIV infection of African nonhuman primates, the lack of clinical disease progression is associated with the presence of double-negative T cells that maintain helper T-cell functions while remaining refractory to viral infection. Moreover, DN T cells may compensate for very low levels of CD4+ T cells observed in a cohort of SIV-infected sooty mangabeys that have remained free of clinical AIDS for over 10 years. These studies identify a potential for double-negative T cells to provide critical helper function during HIV infection.

Double-negative T cells with some CD4+ T-cell functions are associated with a nonpathogenic outcome during SIV infection and represent a potential immune therapeutic target in HIV-infected patients.