Cytokine production and dysregulation in HIV pathogenesis: lessons for development of therapeutics and vaccines

Abstract

Numerous studies have characterized the cytokine modulation observed in human immunodeficiency virus (HIV) infected individuals, from initial infection through chronic disease. Progressive and non-progressive HIV infection models show the cytokine milieu differs in terms of production and responsiveness in these two groups, suggesting an understanding of the role cytokines play during infection is necessary for directing the immune response toward viral control. This review will cover cytokine induction and dysfunction during HIV pathogenesis, with a focus on the interplay between cytokines and transcription factors, T cell activation, and exhaustion. We highlight cytokines that have either vaccine adjuvant or therapeutic potential and discuss the need to identify key factors required for prevention of progression, clearance of infection, or protection from acquisition.

Fig. 1

Transcription factor-induced T cell subset formation and cytokine production. Transcription factors push CD4⁺ and CD8⁺ T cells toward distinct functional phenotypes, thereby influencing the cytokine milieu and direction of the immune response. Th = helper T cell, Tc = cytotoxic T cell, Treg = regulatory T cell, Tfh = T follicular helper cell, T_E = effector T cell, IL = interleukin, IFN = interferon.