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Polymicrobial Sepsis Impairs Antigen-Specific Memory CD4 T Cell-Mediated Immunity.
- Source :
- Frontiers in Immunology; 8/12/2020, Vol. 11, pN.PAG-N.PAG, 16p
- Publication Year :
- 2020
-
Abstract
- Patients who survive sepsis display prolonged immune dysfunction and heightened risk of secondary infection. CD4 T cells support a variety of cells required for protective immunity, and perturbations to the CD4 T cell compartment can decrease overall immune system fitness. Using the cecal ligation and puncture (CLP) mouse model of sepsis, we investigated the impact of sepsis on endogenous Ag-specific memory CD4 T cells generated in C57BL/6 (B6) mice infected with attenuated Listeria monocytogenes (Lm) expressing the I-A<superscript>b</superscript>-restricted 2W1S epitope (Lm-2W). The number of 2W1S-specific memory CD4 T cells was significantly reduced on day 2 after sepsis induction, but recovered by day 14. In contrast to the transient numerical change, the 2W1S-specific memory CD4 T cells displayed prolonged functional impairment after sepsis, evidenced by a reduced recall response (proliferation and effector cytokine production) after restimulation with cognate Ag. To define the extent to which the observed functional impairments in the memory CD4 T cells impacts protection to secondary infection, B6 mice were infected with attenuated Salmonella enterica- 2W (Se -2W) 30 days before sham or CLP surgery, and then challenged with virulent Se- 2W after surgery. Pathogen burden was significantly higher in the CLP-treated mice compared to shams. Similar reductions in functional capacity and protection were noted for the endogenous OVA<subscript>323</subscript>-specific memory CD4 T cell population in sepsis survivors upon Lm-OVA challenge. Our data collectively show CLP-induced sepsis alters the number and function of Ag-specific memory CD4 T cells, which contributes (in part) to the characteristic long-lasting immunoparalysis seen after sepsis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 11
- Database :
- Complementary Index
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 145142230
- Full Text :
- https://doi.org/10.3389/fimmu.2020.01786