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However, the functionally-defined T cell subsets affected by these changes remain poorly characterized. Here, we sought to reveal aberrations in the composition, phenotype and function of canonical T cell subsets in the blood of Systemic Sclerosis (SSc) patients, compared to healthy subjects and Systemic Lupus Erythematosus (SLE) patients.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We developed a novel multidimensional flow-cytometry panel to simultaneously detect lineage-defining transcription factors, co-inhibitory receptors and other functional markers to characterize T cell subsets without\n                    <jats:italic>in vitro<\/jats:italic>\n                    restimulation. We compared T cell landscapes in SSc and SLE patients, and healthy subjects, using Optimized t-SNE and PhenoGraph algorithms. Cytokine production in patient samples was determined using intracellular cytokine staining. Transcriptomic analysis was performed to assess the role of IFN-\u03b3 in fibroblasts.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The data show altered distribution and aberrant functional states of transcription factor-defined T cell subsets in patients with autoimmunity, with shared and unique features between diseases and their subtypes. Strikingly, SSc and SLE patients showed a severe deficiency in subsets of CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>-<\/jats:sup>\n                    CD8\n                    <jats:sup>-<\/jats:sup>\n                    T cells that expressed T-bet, which is critical for IFN-\u03b3-dependent type 1 immunity, and exhibited features of exhaustion. Moreover, TIGIT\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells, known to suppress Th1 responses, were selectively increased in SSc. Functionally, T cells from SSc patients produced less IFN-\u03b3, a cytokine that suppresses pro-fibrotic gene expression in fibroblasts.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study demonstrates that SSc patients have a defective IFN-\u03b3-producing T cell compartment that may lead to reduced anti-fibrotic T cell activity, enabling chronic fibrosis development.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>National Institute of Allergy and Infectious Diseases\/NIH, National Institute of Arthritis and Musculoskeletal Diseases\/NIH, National Heart, Lung and Blood Institute\/NIH, National Scleroderma Foundation, National Jewish Health<\/jats:p>\n                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