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Follicular helper T cells in immunity and systemic autoimmunity

Abstract

Follicular helper T (TFH) cells are essential for B-cell maturation and immunoglobulin production after immunization with thymus-dependent antigens. Nevertheless, the development and function of TFH cells have been less clearly defined than classic CD4+ effector T-cell subsets, including T-helper-1 (TH1), TH2 and TH17 cells. As such, our understanding of the genesis of TFH cells in humans and their role in the development of autoimmunity remains incomplete. However, evidence from animal models of systemic lupus erythematosus (SLE) and patients with systemic autoimmune diseases suggests that these cells are necessary for pathogenic autoantibody production, in a manner analogous to their role in promotion of B-cell maturation during normal immune responses. In this Review, I discuss the findings that have increased our knowledge of TFH-cell development and function in normal and aberrant immune responses. Such information might improve our understanding of autoimmune diseases, such as SLE, and highlights the potential of TFH cells as therapeutic targets in these diseases.

Key Points

  • Follicular helper T (TFH) cells—a subset of CD4+ T cells—are located within the B-cell follicles of secondary lymphoid organs

  • TFH cells are important regulators of B-cell maturation within germinal centres during normal immune responses

  • Characterization of the developmental program of TFH cells could aid their identification and provide insight into the function of these cells in normal and autoimmune responses

  • The transcription factor B-cell lymphoma 6 is both necessary and sufficient for development of TFH cells, controlling expression of molecules essential for TFH-cell trafficking and function

  • TFH cells promote pathogenic autoantibody production in systemic autoimmunity, and potentially represent novel therapeutic targets in autoimmune diseases

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Figure 1: The CD4+ T cell development paradigm.
Figure 2: TFH-cell development and TFH-cell–B-cell collaboration in extrafollicular and GC responses.
Figure 3: The interaction between TFH cells and GC B cells.
Figure 4: Subsets of T cells that promote or regulate B-cell help.

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Acknowledgements

This work was partially supported by NIH grants R01 AR40072, R01 AR44076 and P30 AR053495, and by Rheuminations, Inc. and the Alliance for Lupus Research. The author also acknowledges the many helpful discussions at lab meetings and other forums with his past and present trainees.

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Craft, J. Follicular helper T cells in immunity and systemic autoimmunity. Nat Rev Rheumatol 8, 337–347 (2012). https://doi.org/10.1038/nrrheum.2012.58

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