A Subset of CXCR5+CD8+ T Cells in the Germinal Centers From Human Tonsils and Lymph Nodes Help B Cells Produce Immunoglobulins.

Juan Shen,Huabin Li,Xi Luo,Guanying Xiao,Liantang Wang,Changyou Wu,Jun Huang,Binyan Yang,Qiongli Wu

doi:10.3389/fimmu.2018.02287

Abstract

Recent studies indicated that CXCR5+CD8+ T cells in lymph nodes could eradicate virus-infected target cells. However, in the current study we found that a subset of CXCR5+CD8+ T cells in the germinal centers from human tonsils or lymph nodes are predominately memory cells that express CD45RO and CD27. The involvement of CXCR5+CD8+ T cells in humoral immune responses is suggested by their localization in B cell follicles and by the concomitant expression of costimulatory molecules, including CD40L and ICOS after activation. In addition, CXCR5+CD8+ memory T cells produced significantly higher levels of IL-21, IFN-γ, and IL-4 at mRNA and protein levels compared to CXCR5−CD8+ memory T cells, but IL-21-expressing CXCR5+CD8+ T cells did not express Granzyme B and perforin. When cocultured with sorted B cells, sorted CXCR5+CD8+ T cells promoted the production of antibodies compared to sorted CXCR5−CD8+ T cells. However, fixed CD8+ T cells failed to help B cells and the neutralyzing antibodies against IL-21 or CD40L inhibited the promoting effects of sorted CXCR5+CD8+ T cells on B cells for the production of antibodies. Finally, we found that in the germinal centers of lymph nodes from HIV-infected patients contained more CXCR5+CD8+ T cells compared to normal lymph nodes. Due to their versatile functional capacities, CXCR5+CD8+ T cells are promising candidate cells for immune therapies, particularly when CD4+ T cell help are limited.

Highlights

CD8+ T cells constitute an important branch of adaptive immunity contributing to recognizing viral and bacterial peptides presented by MHC class I molecules on the target cells, and to eliminating of intracellular pathogens and tumors [1,2,3,4,5]
We found that a subset of human CD8+ T cells in tonsils and lymph nodes expressed CXCR5 to localize in B cell follicles
The results showed that 48.7% of CD8+ T cells from tonsils expressed CXCR5, which was significantly higher than those from lymph nodes (23.6%, P < 0.001) and PBMCs (9.16%, P < 0.01) (Figures 1A,B)

Summary

Introduction

CD8+ T cells constitute an important branch of adaptive immunity contributing to recognizing viral and bacterial peptides presented by MHC class I molecules on the target cells, and to eliminating of intracellular pathogens and tumors [1,2,3,4,5]. A subset of CD8+ T cells with high expression of CXCR5 is observed in human secondary lymphoid tissues such as lymph nodes, tonsils and spleens [19,20,21,22,23,24,25]. Those CXCR5+CD8+ T cells possess proinflammatory functions with theraputic potential in multiple inflammatory diseases. The CXCR5+CD8+ T cells presented cytotoxic potential toward virus-infected Tfh cells and B cells, and could be localized in proximity with HIV-infected cells in the lymph nodes from an HIV-infected human subjects [25]

Methods

Results

Conclusion