Cytotoxic CD4 T-cells during HIV infection: Targets or weapons?

Classically, CD4 T-cells have been referred as cytokine-producing cells and important players in immune responses by providing soluble factors that potentiate several effector immune functions. However, it is now evident that CD4 T-cells can also elaborate cytotoxic responses, inducing apoptosis of target cells. Cytotoxic CD4 T cells (CD4 CTLs), exhibit cytolytic functions that resemble those of CD8 T-cells; in fact, there is evidence suggesting that they may have a role in the control of viral infections. In this article, we discuss the role of CD4 CTLs during HIV infection, where CD4 CTLs have been associated with viral control and slow disease progression. In addition, we address the implication of CD4 CTLs in the context of antiretroviral therapy and the partial reconstitution of CD8 T-cells effector function.