Double-negative T cells during HIV/SIV infections: potential pinch hitters in the T-cell lineupSundaravaradan, Vasudhaa; Mir, Kiran D.b; Sodora, Donald L.aCurrent Opinion in HIV and AIDS: March 2012 - Volume 7 - Issue 2 - p 164–171 doi: 10.1097/COH.0b013e3283504a66 FACTORS MODULATING CD4 T-CELL INFECTION: Edited by James Arthos Abstract Author Information Purpose of review 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. Recent findings 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. Summary 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. aSeattle Biomedical Research Institute, Seattle, Washington bEmory University School of Medicine, Atlanta, Georgia, USA Correspondence to Donald L. Sodora, PhD, Associate Member, Seattle Biomedical Research Institute, 307 Westlake Ave., N. Suite 500, Seattle, WA 98109, USA. E-mail: don.sodora@Seattlebiomed.org © 2012 Lippincott Williams & Wilkins, Inc.