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.