The Niche of Follicular Helper T Cells in Systemic Autoimmune Diseases

Eunkyeong Jang; Jeehee Youn

doi:10.7599/hmr.2013.33.1.1

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Jang and Youn: The Niche of Follicular Helper T Cells in Systemic Autoimmune Diseases

Review Article

Hanyang Medical Reviews

Hanyang Medical Reviews 2013; 33(1): 1-9.

Published online: 27 February 2013

DOI: https://doi.org/10.7599/hmr.2013.33.1.1

The Niche of Follicular Helper T Cells in Systemic Autoimmune Diseases

Eunkyeong Jang¹, Jeehee Youn²

¹Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea.

²Department of Anatomy and Cell Biology, Hanyang University College of Medicine, Seoul, Korea.

Correspondence to: Jeehee Youn. Department of Anatomy and Cell Biology, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Korea. Tel: +82-2-2220-0604, Fax: +82-2-2281-7841, jhyoun@hanyang.ac.kr

Received 21 November 2012 Revised 6 January 2013 Accepted 14 January 2013

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Production of thymus-dependent antibodies by autoreactive B cells requires help from T cells. Follicular helper T (Tfh) cells are a unique lineage of CD4⁺ T subsets present in the follicles of peripheral lymphoid tissues which functions primarily to provide help to cognate B cells. Within germinal centers Tfh cells stimulate germinal center B cells to undergo affinity maturation, Ig class switching, and differentiation to memory B cells and plasma cells. Proposals that activity of Tfh cells is crucial for long-lived humoral autoimmunity are supported by the correlation of numbers and/or functions of Tfh cells with disease activity in many autoimmune disorders. In this review, we discuss recent findings regarding Tfh cell development and function. In addition, we discuss putative roles of Tfh cells in the pathogenesis and highlight the potential of Tfh cells as therapeutic targets in autoimmune diseases.

Keywords: T-Lymphocytes, Helper, Autoimmune Diseases, Immunity, Humoral, Germinal Center

Figures and Tables

Fig. 1

Pathways of TD autoantibody production. Autoreactive T and B cells develop in the thymus and bone marrow (BM) and populate in the peripheral lymphoid organs, such as spleen and lymph nodes (LN) (1). In these sites, autoantigen-pulsed dendritic cells license CD4⁺ T cells to differentiate to extrafollicular helper T (Tefh) cells, which in turn activate their cognate B cells to differentiate to antibody-secreting cells (2). In addition to this extra-follicular pathway, more intensive activation and maturation of B cells take place in the germinal center (GC) within the follicle (3). As a result of the GC reaction, affinity matured and isotype switched memory B cells and plasma cells plasma cells (PC) develop, and exit to extra-follicular area (4). Some plasma cells migrate to bone marrow in search of survival niche (5). Autoantibodies infiltrate to target tissues and trigger inflammatory cascades, finally leading to tissue damage (6).

Fig. 2

Development and plasticity of Th subsets. Naïve CD4⁺ T cells differentiate to distinct subsets of effector cells upon priming with antigens. The cytokine milieu during priming is important for selective expression of lineage-specific master transcription factors. Each subset is prone to be converted to others under certain conditions. Th17 conversion to Tfh is speculative to date, so indicated as a broken line.

ACKNOWLEDGEMENTS

This work was supported by a National Research Foundation grant funded by the Korean Government (MEST; 2009-0081790).

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