Attrition of memory CD8 T cells during sepsis requires LFA-1
| Autor: | Craig M. Coopersmith, Lindsay M. Margoles, Kimberly M. Ramonell, John D. Lyons, Kevin W. McConnell, Mara A. Serbanescu, Zhe Liang, Annette Hadley, Mandy L. Ford, Rohit Mittal |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.drug_class medicine.medical_treatment Genes RAG-1 Immunology chemical and pharmacologic phenomena Apoptosis Mice Transgenic Biology CD8-Positive T-Lymphocytes Monoclonal antibody Lymphocyte Activation Immunotherapy Adoptive Sepsis 03 medical and health sciences Mice 0302 clinical medicine T-Lymphocyte Subsets medicine Immunology and Allergy Cytotoxic T cell Animals Lymphocyte function-associated antigen 1 Lymphocyte Count Mice Knockout CD69 T-cell receptor Antibodies Monoclonal Cell Biology Bystander Effect medicine.disease Host Defense & Pathophysiology Lymphocyte Function-Associated Antigen-1 030104 developmental biology Cytokine Models Animal Disease Progression Cytokines Immunologic Memory 030215 immunology |
| Popis: | CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69+CD25intCD62LHI) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain “unactivated” (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis. |
| Databáze: | OpenAIRE |
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