<i>Mycobacterium tuberculosis</i>-specific CD4 T cells expressing transcription factors associate with bacterial control in granulomas
ABSTRACT Despite the extensive research on CD4 T cells within the context ofMycobacterium tuberculosis(Mtb) infection, few studies have focused on identifying and investigating the profile of Mtb-specific T cells within lung granulomas. To facilitate identification of Mtb-specific CD4 T cells, we identified immunodominant epitopes for two Mtb proteins, Rv1196 and Rv0125, using a Mauritian cynomolgus macaque model of Mtb infection, providing data for the synthesis of MHC Class II tetramers. Using tetramers, we identified Mtb-specific cells within different immune compartments post-infection. We found that granulomas were enriched sites for Mtb-specific cells and that tetramer+cells had increased frequencies of the activation marker CD69, and transcription factors T-bet and RORγT, compared to tetramer negative cells within the same sample. Our data revealed that while the frequency of Rv1196 tetramer+cells was positively correlated with granuloma bacterial burden, the frequency of RORγT or T-bet within tetramer+cells was inversely correlated with granuloma bacterial burden highlighting the importance of having activated, functional Mtb-specific cells for control of Mtb in lung granulomas..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 02. Dez. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Grant, Nicole L. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.11.30.518638 |
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| PPN (Katalog-ID): |
XBI038060086 |
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| 520 | |a ABSTRACT Despite the extensive research on CD4 T cells within the context ofMycobacterium tuberculosis(Mtb) infection, few studies have focused on identifying and investigating the profile of Mtb-specific T cells within lung granulomas. To facilitate identification of Mtb-specific CD4 T cells, we identified immunodominant epitopes for two Mtb proteins, Rv1196 and Rv0125, using a Mauritian cynomolgus macaque model of Mtb infection, providing data for the synthesis of MHC Class II tetramers. Using tetramers, we identified Mtb-specific cells within different immune compartments post-infection. We found that granulomas were enriched sites for Mtb-specific cells and that tetramer+cells had increased frequencies of the activation marker CD69, and transcription factors T-bet and RORγT, compared to tetramer negative cells within the same sample. Our data revealed that while the frequency of Rv1196 tetramer+cells was positively correlated with granuloma bacterial burden, the frequency of RORγT or T-bet within tetramer+cells was inversely correlated with granuloma bacterial burden highlighting the importance of having activated, functional Mtb-specific cells for control of Mtb in lung granulomas. | ||
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