Using Primary Immunodeficiencies to Investigate Human CD4<sup>+</sup> T cell Development, Differentiation and Function. — ASN Events
  1. Schedule
  2. Symposium II: Lymphocyte Differentiation, Activation and Memory
  3. Using Primary Immunodeficiencies to Investigate Human CD4+ T cell Development, Differentiation and Function.

Using Primary Immunodeficiencies to Investigate Human CD4+ T cell Development, Differentiation and Function. (#12)

Cindy Ma 1 2 , Kathryn Payne 1 , Lisa Worley 1 2 , Geetha Rao 1 , Danielle T Avery 1 , Bethany Pillay 1 2 , Melanie Wong 3 , Pau Gray 4 , Steven M Holland 5 , Klaus Warnatz 6 , Kaan Boztug 7 , Gulbu Uzel 5 , Jean-Laurent Casanova 8 , Stuart G Tangye 1 2
  1. Immunology Division, Garvan Institute of Medical Research, Sydney, Australia
  2. St Vincent’s Clinical School, UNSW Sydney, Sydney, Australia
  3. Children’s Hospital at Westmead, Sydney, Australia
  4. UNSW Sydney School of Women’s and Children’s Health, Sydney, Australia
  5. Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD, USA
  6. Center for Chronic Immunodeficiency, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  7. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
  8. Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, USA

CD4+ helper T cells play essential and non-redundant roles in cellular and humoral immune responses. As such, the differentiation of naïve CD4+ T helper cells into effector cells is fundamental for host protection against infectious disease. Conversely, dysregulation of CD4+ T cell effector function can lead to significant immunopathologies, including autoimmunity, autoinflammation, allergy and malignancy. Thus, the molecular and cellular mechanisms that govern the induction, maintenance and regulation of CD4+ T cells have to be strictly controlled. While these processes are highly evolved and complex, they remain incompletely defined, especially in the context of human immunology. In order to develop novel therapies for immune-mediated pathologies - infectious diseases, autoimmunity, allergy, malignancies - as well as to improve vaccines and cancer immunosurveillance, it is imperative to identify factors controlling CD4+ T cell function. Here, we use our access to a large and diverse range of patients with primary immunodeficiencies due to monogenic mutations in key genes to determine the transcription factors and cytokine signalling pathways that are essential for the development, differentiation and function of human CD4+ T helper cells and specialised subsets.

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