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

• Published in: Vaccines (Basel) Vol. 11; no. 10; p. 1549
• Main Authors: Armitage, Ellis, Quan, Diana, Flórido, Manuela, Palendira, Umaimainthan, Triccas, James A., Britton, Warwick J.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 29.09.2023; MDPI
• Subjects: Adoptive transfer; Antibodies; Antigens; CD4 antigen; CD4+ T cell; Chemokine receptors; Chemokines; Cloning; Competitive advantage; CXCR3; CXCR3 protein; Cytokines; Epitopes; Experiments; Flow cytometry; Immunization; Immunological memory; Infections; influenza; Influenza A; Lungs; Lymphocytes; Lymphocytes T; Memory cells; mouse; Mucosa; Mycobacterium tuberculosis; Peptides; Public health; pulmonary vaccine; Retention; T cell receptors; Tuberculosis; Vaccines; Viral infections; Viruses; United States > US
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines11101549

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 (TRM) CD4+ T cells in the lungs. The chemokine receptor CXCR3 promotes lung recruitment of T cells, but its role in TRM 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+ T cells in the lungs so that the majority of vaccine-induced CD4+ TRM expresses CXCR3 at 6 weeks. However, CXCR3−/− mice developed equivalent antigen-specific CD4+ T cell responses to wild-type (WT) mice following PR8.p25, and surprisingly retained more p25-specific CD4+ TRM in the lungs than WT mice at 6 weeks. The adoptive transfer of CXCR3−/− and WT P25 T cells into WT mice revealed that the initial recruitment of vaccine-induced CD4+ T cells into the lungs was independent of CXCR3, but by 6 weeks, CXCR3-deficient P25 T cells, and especially CXCR3−/− TRM, were significantly reduced compared to CXCR3-sufficient P25 T cells. Therefore, although CXCR3 was not essential for CD4+ TRM recruitment or retention, it provided a competitive advantage for the induction of M. tuberculosis-specific CD4+ TRM in the lungs following pulmonary immunization.