Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis
Recent data indicate that the differentiation state of Th1 cells determines their protective capacity against tuberculosis. Therefore, we examined the role of Th1-polarizing factors in the generation of protective and non-protective subsets of Mtb-specific Th1 cells. We find that IL-12/23p40 promote...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717303248 |
| _version_ | 1828919580547874816 |
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| author | Michelle A. Sallin Shunsuke Sakai Keith D. Kauffman Howard A. Young Jinfang Zhu Daniel L. Barber |
| author_facet | Michelle A. Sallin Shunsuke Sakai Keith D. Kauffman Howard A. Young Jinfang Zhu Daniel L. Barber |
| author_sort | Michelle A. Sallin |
| collection | DOAJ |
| description | Recent data indicate that the differentiation state of Th1 cells determines their protective capacity against tuberculosis. Therefore, we examined the role of Th1-polarizing factors in the generation of protective and non-protective subsets of Mtb-specific Th1 cells. We find that IL-12/23p40 promotes Th1 cell expansion and maturation beyond the CD73+CXCR3+T-betdim stage, and T-bet prevents deviation of Th1 cells into Th17 cells. Nevertheless, IL- 12/23p40 and T-bet are also essential for the production of a prominent subset of intravascular CX3CR1+KLRG1+ Th1 cells that persists poorly and can neither migrate into the lung parenchyma nor control Mtb growth. Furthermore, T-bet suppresses development of CD69+CD103+ tissue resident phenotype effectors in lung. In contrast, Th1-cell-derived IFN-γ inhibits the accumulation of intravascular CX3CR1+KLRG1+ Th1 cells. Thus, although IL-12 and T-bet are essential host survival factors, they simultaneously oppose lung CD4 T cell responses at several levels, demonstrating the dual nature of Th1 polarization in tuberculosis. |
| first_indexed | 2024-12-13T21:31:45Z |
| format | Article |
| id | doaj.art-06bfe3aba54549109805dc7c8b3325f5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T21:31:45Z |
| publishDate | 2017-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-06bfe3aba54549109805dc7c8b3325f52022-12-21T23:30:48ZengElsevierCell Reports2211-12472017-03-0118133091310410.1016/j.celrep.2017.03.007Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during TuberculosisMichelle A. Sallin0Shunsuke Sakai1Keith D. Kauffman2Howard A. Young3Jinfang Zhu4Daniel L. Barber5T-Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAT-Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAT-Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USACancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USAMolecular and Cellular Immunoregulation Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAT-Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USARecent data indicate that the differentiation state of Th1 cells determines their protective capacity against tuberculosis. Therefore, we examined the role of Th1-polarizing factors in the generation of protective and non-protective subsets of Mtb-specific Th1 cells. We find that IL-12/23p40 promotes Th1 cell expansion and maturation beyond the CD73+CXCR3+T-betdim stage, and T-bet prevents deviation of Th1 cells into Th17 cells. Nevertheless, IL- 12/23p40 and T-bet are also essential for the production of a prominent subset of intravascular CX3CR1+KLRG1+ Th1 cells that persists poorly and can neither migrate into the lung parenchyma nor control Mtb growth. Furthermore, T-bet suppresses development of CD69+CD103+ tissue resident phenotype effectors in lung. In contrast, Th1-cell-derived IFN-γ inhibits the accumulation of intravascular CX3CR1+KLRG1+ Th1 cells. Thus, although IL-12 and T-bet are essential host survival factors, they simultaneously oppose lung CD4 T cell responses at several levels, demonstrating the dual nature of Th1 polarization in tuberculosis.http://www.sciencedirect.com/science/article/pii/S2211124717303248tuberculosisTh1 cellsT-betterminal effectorT cell migrationIL-12 |
| spellingShingle | Michelle A. Sallin Shunsuke Sakai Keith D. Kauffman Howard A. Young Jinfang Zhu Daniel L. Barber Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis Cell Reports tuberculosis Th1 cells T-bet terminal effector T cell migration IL-12 |
| title | Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis |
| title_full | Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis |
| title_fullStr | Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis |
| title_full_unstemmed | Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis |
| title_short | Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis |
| title_sort | th1 differentiation drives the accumulation of intravascular non protective cd4 t cells during tuberculosis |
| topic | tuberculosis Th1 cells T-bet terminal effector T cell migration IL-12 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717303248 |
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