Cindy S Ma1, Gulbu Uzel, Stuart G Tangye. 1. aImmunology Division, Garvan Institute of Medical Research, Darlinghurst bSt Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia cLaboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
Abstract
PURPOSE OF REVIEW: To summarize our understanding of the biology of T follicular helper (Tfh) cells and how insights into this are being provided by the study of human monogenic immunological diseases. RECENT FINDINGS: Antibody production is a key feature of the vertebrate immune system. Antibodies neutralize and clear pathogens, thereby protecting against infectious diseases. Long-lived humoral immunity depends on help provided by Tfh cells, which support the differentiation of antigen-specific B cells into memory and plasma cells. Tfh cells are generated from naïve CD4 T cells following the receipt of inputs from various cell surface receptors. Although genetically modified mice have provided a great understanding of the requirements for generating Tfh cells, it is critical that the requirements for human Tfh cells are also established. This is being achieved by the systematic analysis of humans with monogenic mutations that cause primary immunodeficiencies characterized by impaired humoral immunity following infection or vaccination. SUMMARY: The elucidation of the mechanisms that regulate Tfh cell generation, differentiation and function should reveal targets for novel therapeutics that may offer opportunities to manipulate these cells to not only improve humoral immunity in the setting of primary immunodeficiencies but also temper their dysregulation in conditions of antibody-mediated autoimmunity.
PURPOSE OF REVIEW: To summarize our understanding of the biology of T follicular helper (Tfh) cells and how insights into this are being provided by the study of human monogenic immunological diseases. RECENT FINDINGS: Antibody production is a key feature of the vertebrate immune system. Antibodies neutralize and clear pathogens, thereby protecting against infectious diseases. Long-lived humoral immunity depends on help provided by Tfh cells, which support the differentiation of antigen-specific B cells into memory and plasma cells. Tfh cells are generated from naïve CD4 T cells following the receipt of inputs from various cell surface receptors. Although genetically modified mice have provided a great understanding of the requirements for generating Tfh cells, it is critical that the requirements for human Tfh cells are also established. This is being achieved by the systematic analysis of humans with monogenic mutations that cause primary immunodeficiencies characterized by impaired humoral immunity following infection or vaccination. SUMMARY: The elucidation of the mechanisms that regulate Tfh cell generation, differentiation and function should reveal targets for novel therapeutics that may offer opportunities to manipulate these cells to not only improve humoral immunity in the setting of primary immunodeficiencies but also temper their dysregulation in conditions of antibody-mediated autoimmunity.
Authors: Cindy S Ma; Natalie Wong; Geetha Rao; Danielle T Avery; James Torpy; Thomas Hambridge; Jacinta Bustamante; Satoshi Okada; Jennifer L Stoddard; Elissa K Deenick; Simon J Pelham; Kathryn Payne; Stéphanie Boisson-Dupuis; Anne Puel; Masao Kobayashi; Peter D Arkwright; Sara Sebnem Kilic; Jamila El Baghdadi; Shigeaki Nonoyama; Yoshiyuki Minegishi; Seyed Alireza Mahdaviani; Davood Mansouri; Aziz Bousfiha; Annaliesse K Blincoe; Martyn A French; Peter Hsu; Dianne E Campbell; Michael O Stormon; Melanie Wong; Stephen Adelstein; Joanne M Smart; David A Fulcher; Matthew C Cook; Tri Giang Phan; Polina Stepensky; Kaan Boztug; Aydan Kansu; Aydan İkincioğullari; Ulrich Baumann; Rita Beier; Tony Roscioli; John B Ziegler; Paul Gray; Capucine Picard; Bodo Grimbacher; Klaus Warnatz; Steven M Holland; Jean-Laurent Casanova; Gulbu Uzel; Stuart G Tangye Journal: J Allergy Clin Immunol Date: 2015-07-07 Impact factor: 10.793