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J Clin Immunol ; 41(8): 1794-1803, 2021 11.
Article in English | MEDLINE | ID: mdl-34389889

ABSTRACT

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome mainly caused by uncontrolled activation of antigen presenting cells and CD8 T cells. CD8 T cell exhaustion is a known phenomenon in chronic viral infections and cancer. However, the role of T cell exhaustion is not yet identified in HLH in the background of persistent inflammation. So, currently, we have characterized the CD8 T cells using flow cytometry to understand the phenomenon of exhaustion in these cells in HLH. METHODS: We have comprehensively evaluated lymphocyte subsets and characterized CD8 T cells using immunophenotypic markers like PD1, TIM3, LAG3, Ki67, Granzyme B, etc. in a cohort of 21 HLH patients. Effector cytokine secretion and degranulation by CD8 T cells are also studied. RESULTS: Our findings indicate skewed lymphocyte subsets and aberrantly activated CD8 T cells in HLH. CD8 T cells exhibit significantly increased expression of PD1, TIM3, and LAG3 prominently in primary HLH as compared to controls. PD1 + CD8 T cells express elevated levels of Granzyme B and Ki67. Moreover, CD8 T cells are hypofunctional as evidenced by significantly reduced cytokine secretion and compromised CD107a degranulation. CONCLUSION: The study has revealed that CD8 + cytotoxic T lymphocytes from HLH patients exhibited high expression of exhaustion markers with overall impaired function. To the best of our understanding, this is the first report suggesting functional exhaustion of CD8 T cells in both primary and secondary HLH. Future studies to understand the association of exhaustion with disease outcome are needed for its probable therapeutic implementation.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Lymphohistiocytosis, Hemophagocytic/immunology , Adolescent , Adult , Aged , Antigens, CD/immunology , Child , Child, Preschool , Cytokines/immunology , Female , Granzymes/immunology , Hepatitis A Virus Cellular Receptor 2/immunology , Humans , Infant , Ki-67 Antigen/immunology , Male , Middle Aged , Phenotype , Programmed Cell Death 1 Receptor/immunology , Young Adult , Lymphocyte Activation Gene 3 Protein
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