Immunologic Research

, Volume 57, Issue 1–3, pp 279–291 | Cite as

Interleukin-21 and T follicular helper cells in HIV infection: research focus and future perspectives

  • Suresh Pallikkuth
  • Savita Pahwa
Immunology & Microbiology in Miami


Interleukin (IL)-21 is a member of the γ chain-receptor cytokine family along with IL-2, IL-4, IL-7, IL-9, and IL-15. The effects of IL-21 are pleiotropic, owing to the broad cellular distribution of the IL-21 receptor. IL-21 is secreted by activated CD4 T cells and natural killer T cells. Within CD4 T cells, its secretion is restricted mainly to T follicular helper (Tfh) cells and Th17 cells to a lesser extent. Our research focus has been on the role of IL-21 and more recently of Tfh in immunopathogenesis of HIV infection. This review focuses on first the influence of IL-21 in regulation of T cell, B cell, and NK cell responses and its immunotherapeutic potential in viral infections and as a vaccine adjuvant. Second, we discuss the pivotal role of Tfh in generation of antibody responses in HIV-infected persons in studies using influenza vaccines as a probe. Lastly, we review data supporting ability of HIV to infect Tfh and the role of these cells as reservoirs for HIV and their contribution to viral persistence.


IL-21 and T cells Tfh cells IL-21 and B cells HIV persistence HIV and IL-21 IL-21 and immunity 



This work was supported by NIH Grant A1077501, AI 108472 to SP and a CFAR developmental award to S Palli. We acknowledge support from the Miami Center for AIDS Research (CFAR) at the University Of Miami Miller School Of Medicine, which is funded by a Grant (P30AI073961) from the National Institutes of Health (NIH). The CFAR program at the NIH includes the following co-funding and participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR.

Conflict of interest

The authors have no financial conflicts of interest.


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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyUniversity of Miami Miller School of MedicineMiamiUSA

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