Purpose of review: To understand the role of HIV-specific CD4 T cells in viral control and highlight recent progress in the field.
Recent findings: HIV-specific CD4 T cells show higher functional avidity in elite controllers than in patients with progressive infection. There is an attrition of the HIV-specific CD4 T-cell population in the digestive mucosa of antiretroviral therapy (ART)-treated patients that contrasts with robust responses in individuals with spontaneous viral control. Secretion of the cytokine IL-21, by HIV-specific CD4 T cells, is associated with disease control and enhances the capacity of HIV-specific CD8 T cells to suppress viral replication. Studies of the PD-1, IL-10, and Tim-3 pathways provided insight into mechanisms of HIV-specific CD4 T-cell exhaustion and new evidence that manipulation of these networks may restore immune functions. Robust, polyfunctional CD4 T-cell responses can be elicited with novel HIV and simian immunodeficiency virus (SIV) vaccines.
Summary: These observations show that HIV-specific CD4 T-cell responses are different in elite controllers and individuals with progressive disease. Evidence suggests that HIV-specific CD4 T cells will be an important component of an effective HIV vaccine and significant efforts need to be made to further our understanding of HIV-specific CD4 T-cell functions in different body compartments.
aRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, USA
bDivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA
Correspondence to Daniel E. Kaufmann, MD, Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital East, Room 5239, 149 13th Street, Charlestown, Boston, MA 02129, USA Tel: +1 617 726 8630; fax: +1 617 726 5411; e-mail: firstname.lastname@example.org