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CXCR3 Provides a Competitive Advantage for Retention of Mycobacterium tuberculosis -Specific Tissue-Resident Memory T Cells Following a Mucosal Tuberculosis Vaccine.

Authors :
Armitage E
Quan D
Flórido M
Palendira U
Triccas JA
Britton WJ
Source :
Vaccines [Vaccines (Basel)] 2023 Sep 29; Vol. 11 (10). Date of Electronic Publication: 2023 Sep 29.
Publication Year :
2023

Abstract

Mycobacterium tuberculosis is a major human pathogen, and new vaccines are needed to prevent transmission. Mucosal vaccination may confer protection against M. tuberculosis by stimulating tissue-resident memory (T <subscript>RM</subscript> ) CD4 <superscript>+</superscript> T cells in the lungs. The chemokine receptor CXCR3 promotes lung recruitment of T cells, but its role in T <subscript>RM</subscript> development is unknown. This study demonstrates the recombinant influenza A virus vaccine PR8.p25, expressing the immunodominant M. tuberculosis T cell epitope p25, induces CXCR3 expression on p25-specific CD4 <superscript>+</superscript> T cells in the lungs so that the majority of vaccine-induced CD4 <superscript>+</superscript> T <subscript>RM</subscript> expresses CXCR3 at 6 weeks. However, CXCR3 <superscript>-/-</superscript> mice developed equivalent antigen-specific CD4 <superscript>+</superscript> T cell responses to wild-type (WT) mice following PR8.p25, and surprisingly retained more p25-specific CD4 <superscript>+</superscript> T <subscript>RM</subscript> in the lungs than WT mice at 6 weeks. The adoptive transfer of CXCR3 <superscript>-/-</superscript> and WT P25 T cells into WT mice revealed that the initial recruitment of vaccine-induced CD4 <superscript>+</superscript> T cells into the lungs was independent of CXCR3, but by 6 weeks, CXCR3-deficient P25 T cells, and especially CXCR3 <superscript>-/-</superscript> T <subscript>RM</subscript> , were significantly reduced compared to CXCR3-sufficient P25 T cells. Therefore, although CXCR3 was not essential for CD4 <superscript>+</superscript> T <subscript>RM</subscript> recruitment or retention, it provided a competitive advantage for the induction of M. tuberculosis -specific CD4 <superscript>+</superscript> T <subscript>RM</subscript> in the lungs following pulmonary immunization.

Details

Language :
English
ISSN :
2076-393X
Volume :
11
Issue :
10
Database :
MEDLINE
Journal :
Vaccines
Publication Type :
Academic Journal
Accession number :
37896952
Full Text :
https://doi.org/10.3390/vaccines11101549