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Review
. 2018 May 22:9:1095.
doi: 10.3389/fimmu.2018.01095. eCollection 2018.

Differentiation and Function of Follicular CD8 T Cells During Human Immunodeficiency Virus Infection

Minglu Xiao  1 , Xiangyu Chen  1 , Ran He  2 , Lilin Ye  1
Affiliations
Review

Differentiation and Function of Follicular CD8 T Cells During Human Immunodeficiency Virus Infection

Minglu Xiao et al. Front Immunol. .

Abstract

The combination antiretroviral therapeutic (cART) regime effectively suppresses human immunodeficiency virus (HIV) replication and prevents progression to acquired immunodeficiency diseases. However, cART is not a cure, and viral rebound will occur immediately after treatment is interrupted largely due to the long-term presence of an HIV reservoir that is composed of latently infected target cells that maintain a quiescent state or persistently produce infectious viruses. CD4 T cells that reside in B-cell follicles within lymphoid tissues, called follicular helper T cells (TFH), have been identified as a major HIV reservoir. Due to their specialized anatomical structure, HIV-specific CD8 T cells are largely insulated from this TFH reservoir. It is increasingly clear that the elimination of TFH reservoirs is a key step toward a functional cure for HIV infection. Recently, several studies have suggested that a fraction of HIV-specific CD8 T cells can differentiate into a CXCR5-expressing subset, which are able to migrate into B-cell follicles and inhibit viral replication. In this review, we discuss the differentiation and functions of this newly identified CD8 T-cell subset and propose potential strategies for purging TFH HIV reservoirs by utilizing this unique population.

Keywords: B-cell follicles; CXCR5+CD8 T cells; follicular CD8 T cells; human immunodeficiency virus infections; human immunodeficiency virus reservoir.

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Figures

Figure 1
Figure 1
Comparison of CXCR5+CD8 T cells in lymphocytic choromeningitis virus (LCMV)-Cl13 and human immunodeficiency virus (HIV) infection. In chronic LCMV-Cl13 infection, viruses seldom infect B-cell follicles, thus B-cell follicles function as a sanctuary for CXCR5+CD8 T cells to prevent rapid exhaustion. In contrast, HIV virus preferentially targets TFH cells in B-cell follicles for productive and latent infection, thus accumulating high antigen loads in B-cell follicles may drive more severe exhaustion of CXCR5+CD8 T cells.
Figure 2
Figure 2
Potential strategies for employing CXCR5+CD8 T cells to purge human immunodeficiency virus (HIV) reservoirs in B cell follicles. (A) Adoptive transfer of in vitro expanded endogenous CXCR5+CD8 T cells from blood. As CXCR5+CD8 T cells from peripheral blood will further differentiate into CXCR5−CD8 T cells upon antigen re-stimulation, the development of in vitro culturing conditions optimal for both expanding and preserving the migratory and functional characteristics of CXCR5+CD8 T cells should be a focus for future investigations. (B) Transfer genetically modified virus-specific CD8 T cells over-expressing transcriptional factors that promote the differentiation and lineage stabilization of CXCR5+CD8 T cells. (C) Programmed cell death-1 pathway blockade may effectively expand transferred virus-specific CXCR5+CD8 T cells and boost the effector functions.
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