Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells
Evaluation of sepsis-induced immunoparalysis has highlighted how decreased lymphocyte number/function contribute to worsened infection/cancer. Yet, an interesting contrast exists with autoimmune disease development, wherein diminishing pathogenic effectors may benefit the post-septic host. Within th...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-11-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/55800 |
| _version_ | 1811181462040346624 |
|---|---|
| author | Isaac J Jensen Samantha N Jensen Frances V Sjaastad Katherine N Gibson-Corley Thamothrampillai Dileepan Thomas S Griffith Ashutosh K Mangalam Vladimir P Badovinac |
| author_facet | Isaac J Jensen Samantha N Jensen Frances V Sjaastad Katherine N Gibson-Corley Thamothrampillai Dileepan Thomas S Griffith Ashutosh K Mangalam Vladimir P Badovinac |
| author_sort | Isaac J Jensen |
| collection | DOAJ |
| description | Evaluation of sepsis-induced immunoparalysis has highlighted how decreased lymphocyte number/function contribute to worsened infection/cancer. Yet, an interesting contrast exists with autoimmune disease development, wherein diminishing pathogenic effectors may benefit the post-septic host. Within this framework, the impact of cecal ligation and puncture (CLP)-induced sepsis on the development of experimental autoimmune encephalomyelitis (EAE) was explored. Notably, CLP mice have delayed onset and reduced disease severity, relative to sham mice. Reduction in disease severity was associated with reduced number, but not function, of autoantigen (MOG)-specific pathogenic CD4 T cells in the CNS during disease and draining lymph node during priming. Numerical deficits of CD4 T cell effectors are associated with the loss of MOG-specific naive precursors. Critically, transfer of MOG-TCR transgenic (2D2) CD4 T cells after, but not before, CLP led to EAE disease equivalent to sham mice. Thus, broad impairment of antigenic responses, including autoantigens, is a hallmark of sepsis-induced immunoparalysis. |
| first_indexed | 2024-04-11T09:18:08Z |
| format | Article |
| id | doaj.art-791eeaac056e44cd9c5088f9d81705e1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:18:08Z |
| publishDate | 2020-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-791eeaac056e44cd9c5088f9d81705e12022-12-22T04:32:16ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.55800Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cellsIsaac J Jensen0https://orcid.org/0000-0002-3107-3961Samantha N Jensen1https://orcid.org/0000-0002-3001-5217Frances V Sjaastad2Katherine N Gibson-Corley3Thamothrampillai Dileepan4Thomas S Griffith5https://orcid.org/0000-0002-7205-9859Ashutosh K Mangalam6Vladimir P Badovinac7https://orcid.org/0000-0003-3180-2439Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, United StatesInterdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, United StatesMicrobiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, United StatesDepartment of Pathology, University of Iowa, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, United StatesDepartment of Microbiology and Immunology, University of Minnesota, Center for Immunology, Minneapolis, United StatesMicrobiology, Immunology, and Cancer Biology PhD Program, Department of Urology, Center for Immunology, Minneapolis VA Health Care System, University of Minnesota, Minneapolis, United StatesInterdisciplinary Graduate Program in Immunology, Department of Pathology, University of Iowa, Iowa City, United StatesInterdisciplinary Graduate Program in Immunology, Department of Pathology, Department of Microbiology and Immunology, University of Iowa, Iowa City, United StatesEvaluation of sepsis-induced immunoparalysis has highlighted how decreased lymphocyte number/function contribute to worsened infection/cancer. Yet, an interesting contrast exists with autoimmune disease development, wherein diminishing pathogenic effectors may benefit the post-septic host. Within this framework, the impact of cecal ligation and puncture (CLP)-induced sepsis on the development of experimental autoimmune encephalomyelitis (EAE) was explored. Notably, CLP mice have delayed onset and reduced disease severity, relative to sham mice. Reduction in disease severity was associated with reduced number, but not function, of autoantigen (MOG)-specific pathogenic CD4 T cells in the CNS during disease and draining lymph node during priming. Numerical deficits of CD4 T cell effectors are associated with the loss of MOG-specific naive precursors. Critically, transfer of MOG-TCR transgenic (2D2) CD4 T cells after, but not before, CLP led to EAE disease equivalent to sham mice. Thus, broad impairment of antigenic responses, including autoantigens, is a hallmark of sepsis-induced immunoparalysis.https://elifesciences.org/articles/55800sepsisEAECD4 T cellsimmunoparalysisadoptive transfer |
| spellingShingle | Isaac J Jensen Samantha N Jensen Frances V Sjaastad Katherine N Gibson-Corley Thamothrampillai Dileepan Thomas S Griffith Ashutosh K Mangalam Vladimir P Badovinac Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells eLife sepsis EAE CD4 T cells immunoparalysis adoptive transfer |
| title | Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
| title_full | Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
| title_fullStr | Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
| title_full_unstemmed | Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
| title_short | Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
| title_sort | sepsis impedes eae disease development and diminishes autoantigen specific naive cd4 t cells |
| topic | sepsis EAE CD4 T cells immunoparalysis adoptive transfer |
| url | https://elifesciences.org/articles/55800 |
| work_keys_str_mv | AT isaacjjensen sepsisimpedeseaediseasedevelopmentanddiminishesautoantigenspecificnaivecd4tcells AT samanthanjensen sepsisimpedeseaediseasedevelopmentanddiminishesautoantigenspecificnaivecd4tcells AT francesvsjaastad sepsisimpedeseaediseasedevelopmentanddiminishesautoantigenspecificnaivecd4tcells AT katherinengibsoncorley sepsisimpedeseaediseasedevelopmentanddiminishesautoantigenspecificnaivecd4tcells AT thamothrampillaidileepan sepsisimpedeseaediseasedevelopmentanddiminishesautoantigenspecificnaivecd4tcells AT thomassgriffith sepsisimpedeseaediseasedevelopmentanddiminishesautoantigenspecificnaivecd4tcells AT ashutoshkmangalam sepsisimpedeseaediseasedevelopmentanddiminishesautoantigenspecificnaivecd4tcells AT vladimirpbadovinac sepsisimpedeseaediseasedevelopmentanddiminishesautoantigenspecificnaivecd4tcells |