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GPA33 is expressed on multiple human blood cell types and distinguishes CD4+ central memory T cells with and without effector function |
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| Authors: | Rianne Opstelten Jessica S Suwandi Manon C. Slot Florencia Morgana Andrew M Scott Sandra Laban Tatjana Nikolic Annelies W Turksma Anna Kroeze Carlijn Voermans Jaap-Jan Zwaginga Bart O Roep Derk Amsen |
| Affiliation: | 1. Department of Hematopoiesis and Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands;2. Immunomodulation and Regenerative Cell Therapy, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands;3. Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La Trobe University, Melbourne, Australia;4. Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands;5. Department of Hematopoiesis and Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands;6. Immunomodulation and Regenerative Cell Therapy, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands Sanquin Research, Center for Clinical Transfusion Research and Jon J van Rood Center for Clinical Transfusion Science, Leiden University Medical Center, Leiden, Netherlands;7. Immunomodulation and Regenerative Cell Therapy, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands Department of Diabetes Immunology, Diabetes & Metabolism Research Institute at the Beckman Research Institute, City of Hope, Duarte, CA, USA |
| Abstract: | The Ig superfamily protein glycoprotein A33 (GPA33) has been implicated in immune dysregulation, but little is known about its expression in the immune compartment. Here, we comprehensively determined GPA33 expression patterns on human blood leukocyte subsets, using mass and flow cytometry. We found that GPA33 was expressed on fractions of B, dendritic, natural killer and innate lymphoid cells. Most prominent expression was found in the CD4+ T cell compartment. Naïve and CXCR5+ regulatory T cells were GPA33high, and naïve conventional CD4+ T cells expressed intermediate GPA33 levels. The expression pattern of GPA33 identified functional heterogeneity within the CD4+ central memory T cell (Tcm) population. GPA33+ CD4+ Tcm cells were fully undifferentiated, bona fide Tcm cells that lack immediate effector function, whereas GPA33– Tcm cells exhibited rapid effector functions and may represent an early stage of differentiation into effector/effector memory T cells before loss of CD62L. Expression of GPA33 in conventional CD4+ T cells suggests a role in localization and/or preservation of an undifferentiated state. These results form a basis to study the function of GPA33 and show it to be a useful marker to discriminate between different cellular subsets, especially in the CD4+ T cell lineage. |
| Keywords: | antibody therapy CD4+ T cell differentiation CyTOF flow cytometry human glycoprotein A33 |