CD8⁺GITR⁺ T cells may negatively regulate T cell overactivation in aplastic anemia

ABSTRACT

Aplastic anemia (AA) is a T cell immune-mediated autoimmune disease. Overactivated CD8⁺ T cells play a leading role in the pathogenesis of AA, which may be due to disbalance in costimulatory and coinhibitory signals in T cells. In this study, we firstly investigated the expression of OX40, 4–1BB, GITR, ICOS, CTLA-4, LAG-3, and TIM-3 on CD8⁺ T cells from untreated patients with AA and healthy individuals (HIs) by flow cytometry. Moreover, we further analyzed the phenotype and functional characteristics of CD8⁺GITR⁺ T cells to more fully assess the T cell activation dysfunction in AA. We for the first time demonstrated significantly decreased percentage of CD8⁺GITR⁺ T cells in AA, and CD8⁺GITR⁺CTLA-4⁺ T cells were significantly higher in patients with AA compared with HIs. Conversely, the percentage of CD8⁺GITR⁺granzyme B⁺ and CD8⁺GITR⁺perforin⁺ T cells in AA patients was significantly reduced. Our preliminary data illustrate that the CD8⁺GITR⁺ T cell population might negatively regulate overactive T cell activation in AA.

KEYWORDS:

• Aplastic anemia
• T cell activation
• glucocorticoid-induced tumor necrosis factor receptor

Abbreviations

AA: aplastic anemia; CTLA-4: cytotoxic T-lymphocyte-associated antigen 4; GITR: glucocorticoid-induced tumor necrosis factor receptor; GITRL: glucocorticoid-induced tumor necrosis factor receptor ligand; HIs: healthy individuals; ICOS: inducible T cell costimulator; LAG-3: lymphocyte activation gene-3; NSAA: non-severe aplastic anemia; PB: peripheral blood; PD-1: programmed cell death protein 1; SAA: severe aplastic anemia; TIM-3: T cell immunoglobulin and mucin domain 3; TNFR: tumor necrosis factor receptor; VSAA: very severe aplastic anemia

Acknowledgments

We thank the Flow Facility of Biological Translational Research Institute, Jinan University.

Authors’ contributions

BL and YQL contributed to the concept development, provided the study design, coordinated the study, and drafted the manuscript. GXH performed flow cytometry, data analysis, and prepared figures and the table. YPZ, XLW, ZY, JL, QS, XHC, CTC, WFL, MZ, and YML provided the samples and clinical data. All authors read and approved the final manuscript.

Ethics approval and consent to participate

All PB samples were obtained with consent. The study was approved by the Ethics Committee of School of Medicine of Jinan University. Written informed consent was obtained from patients in accordance with the Helsinki Declaration.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (Nos. 81370605, 81702082, and 81460026), the Natural Science Foundation of Guangdong province (Nos. S201201000879 and 2017A030313852), Science and Information Technology of Guangzhou funded basic research for application project (No. 2014A020212209 and 2020A151501042) and Medical Scientific Research Foundation of Guangdong Province of China (No. A20190346).