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- Title
Distinct CD8 T Cell Populations with Differential Exhaustion Profiles Associate with Secondary Complications in Common Variable Immunodeficiency.
- Authors
Klocperk, Adam; Friedmann, David; Schlaak, Alexandra Emilia; Unger, Susanne; Parackova, Zuzana; Goldacker, Sigune; Sediva, Anna; Bengsch, Bertram; Warnatz, Klaus
- Abstract
Purpose: Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency, with heterogeneous clinical presentation. Our goal was to analyze CD8 T cell homeostasis in patients with infection only CVID, compared to those additionally affected by dysregulatory and autoimmune phenomena. Methods: We used flow and mass cytometry evaluation of peripheral blood of 40 patients with CVID and 17 healthy donors. Results: CD8 T cells are skewed in patients with CVID, with loss of naïve and increase of effector memory stages, expansion of cell clusters with high functional exhaustion scores, and a highly activated population of cells with immunoregulatory features, producing IL-10. These findings correlate to clinically widely used B cell-based EURO classification. Features of exhaustion, including loss of CD127 and CD28, and expression of TIGIT and PD-1 in CD8 T cells are strongly associated with interstitial lung disease and autoimmune cytopenias, whereas CD8 T cell activation with elevated HLA-DR and CD38 expression predict non-infectious diarrhea. Conclusion: We demonstrate features of advanced differentiation, exhaustion, activation, and immunoregulatory capabilities within CD8 T cells of CVID patients. Assessment of CD8 T cell phenotype may allow risk assessment of CVID patients and provide new insights into CVID pathogenesis, including a better understanding of mechanisms underlying T cell exhaustion and regulation.
- Subjects
COMMON variable immunodeficiency; T cells; FATIGUE (Physiology); CELL populations; CD8 antigen; SEVERE combined immunodeficiency
- Publication
Journal of Clinical Immunology, 2022, Vol 42, Issue 6, p1254
- ISSN
0271-9142
- Publication type
Article
- DOI
10.1007/s10875-022-01291-9