General autoimmunity

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Immunophenotypic Heterogeneity of Regulatory and Helper T Lymphocytes in Patients with Genetic Autoimmunities

Thursday, June 15
5:45 PM - 7:00 PM

Immunological studies of patients with genetic immune mediated disease with autoimmunity offer a unique opportunity to understand the role of regulatory T (Treg) cells in immune homeostasis. IPEX and CTLA-4 deficiency are examples of mono-genetic diseases presenting with severe autoimmunity. Treg cells maintain self-tolerance, and their impaired function in CTLA-4 deficient and IPEX patients leads to the characteristic clinical phenotype. Human CD4+ CD25hi CD127lo/- FOXP3+ regulatory T (Treg) cells express both CTLA-4 and FOXP3 constitutively, which are dysfunctional in CTLA-4 deficient and IPEX patients, respectively. Furthermore, low frequency of Treg cells can also result in autoimmunity in other primary immunodeficiencies, such as DiGeorge syndrome (DGS).


To study patients with immune dysregulation we have combined the use of mass cytometry (CyTOF), with functional assays. Using CyTOF, we can perform a comprehensive analysis of CD4+ Treg and T helper (Th) type 1 (Th1), Th2, Th17 and follicular T helper (Tfh) cells on a single patient sample. This allows us to evaluate how the detected alterations in CD4+ T cell subpopulations correlate with autoimmunity due to different single mutations with overlapping clinical phenotype.


The IPEX patients analyzed showed increased Treg cell frequency with low FOXP3 expression compared to age-matched healthy controls. In contrast, DGS and CTLA-4 deficient patients had normal FOXP3 expression, but a low frequency of Treg cells. Each disease, however, had a unique signature of abnormal Th1, Th2, Th17, and Tfh cell frequency and function, providing new insights into each disease mechanism.

Matthew Kunicki

Life Science Research Professional I
Institute of Stem Cell Biology and Regenerative Medicine, Stanford University

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    Nicholas Harre

    University of California Los Angeles

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      Laura Amaya

      Institute of Stem Cell Biology and Regenerative Medicine, Stanford University

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        Katja Weinacht

        Assistant Professor
        Institute of Stem Cell Biology and Regenerative Medicine, Stanford University

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          Kenneth Weinberg

          Professor
          Institute of Stem Cell Biology and Regenerative Medicine, Stanford University

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            Rosa Bacchetta

            Associate Professor
            Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford University

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              Maria-Grazia Roncarolo

              Professor
              Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford University

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                Immunophenotypic Heterogeneity of Regulatory and Helper T Lymphocytes in Patients with Genetic Autoimmunities



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