tetano
Editor, Senior Moderator
Mucosal Immunol. 2018 Aug 16. doi: 10.1038/s41385-018-0065-9. [Epub ahead of print]
[h=1]Pulmonary immunization with a recombinant influenza A virus vaccine induces lung-resident CD4[SUP]+[/SUP] memory T cells that are associated with protection against tuberculosis.[/h] Fl?rido M[SUP]1[/SUP], Muflihah H[SUP]1[/SUP], Lin LCW[SUP]1[/SUP], Xia Y[SUP]2[/SUP], Sierro F[SUP]3,[/SUP][SUP]4[/SUP], Palendira M[SUP]1,[/SUP][SUP]5[/SUP], Feng CG[SUP]1,[/SUP][SUP]5[/SUP], Bertolino P[SUP]3,[/SUP][SUP]6[/SUP], Stambas J[SUP]2[/SUP], Triccas JA[SUP]1,[/SUP][SUP]5[/SUP], Britton WJ[SUP]7,[/SUP][SUP]8,[/SUP][SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The lung is the primary site of infection with the major human pathogen, Mycobacterium tuberculosis. Effective vaccines against M. tuberculosis must stimulate memory T cells to provide early protection in the lung. Recently, tissue-resident memory T cells (T[SUB]RM[/SUB]) were found to be phenotypically and transcriptional distinct from circulating memory T cells. Here, we identified M. tuberculosis-specific CD4[SUP]+[/SUP] T cells induced by recombinant influenza A viruses (rIAV) vaccines expressing M. tuberculosis peptides that persisted in the lung parenchyma with the phenotypic and transcriptional characteristics of T[SUB]RMs[/SUB]. To determine if these rIAV-induced CD4[SUP]+[/SUP] T[SUB]RM[/SUB] were protective independent of circulating memory T cells, mice previously immunized with the rIAV vaccine were treated with the sphingosine-1-phosphate receptor modulator, FTY720, prior to and during the first 17 days of M. tuberculosis challenge. This markedly reduced circulating T cells, but had no effect on the frequency of M. tuberculosis-specific CD4[SUP]+[/SUP] T[SUB]RMs[/SUB] in the lung parenchyma or their cytokine response to infection. Importantly, mice immunized with the rIAV vaccine were protected against M. tuberculosis infection even when circulating T cells were profoundly depleted by the treatment. Therefore, pulmonary immunization with the rIAV vaccine stimulates lung-resident CD4[SUP]+[/SUP] memory T cells that are associated with early protection against tuberculosis infection.
PMID: 30115996 DOI: 10.1038/s41385-018-0065-9
[h=1]Pulmonary immunization with a recombinant influenza A virus vaccine induces lung-resident CD4[SUP]+[/SUP] memory T cells that are associated with protection against tuberculosis.[/h] Fl?rido M[SUP]1[/SUP], Muflihah H[SUP]1[/SUP], Lin LCW[SUP]1[/SUP], Xia Y[SUP]2[/SUP], Sierro F[SUP]3,[/SUP][SUP]4[/SUP], Palendira M[SUP]1,[/SUP][SUP]5[/SUP], Feng CG[SUP]1,[/SUP][SUP]5[/SUP], Bertolino P[SUP]3,[/SUP][SUP]6[/SUP], Stambas J[SUP]2[/SUP], Triccas JA[SUP]1,[/SUP][SUP]5[/SUP], Britton WJ[SUP]7,[/SUP][SUP]8,[/SUP][SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The lung is the primary site of infection with the major human pathogen, Mycobacterium tuberculosis. Effective vaccines against M. tuberculosis must stimulate memory T cells to provide early protection in the lung. Recently, tissue-resident memory T cells (T[SUB]RM[/SUB]) were found to be phenotypically and transcriptional distinct from circulating memory T cells. Here, we identified M. tuberculosis-specific CD4[SUP]+[/SUP] T cells induced by recombinant influenza A viruses (rIAV) vaccines expressing M. tuberculosis peptides that persisted in the lung parenchyma with the phenotypic and transcriptional characteristics of T[SUB]RMs[/SUB]. To determine if these rIAV-induced CD4[SUP]+[/SUP] T[SUB]RM[/SUB] were protective independent of circulating memory T cells, mice previously immunized with the rIAV vaccine were treated with the sphingosine-1-phosphate receptor modulator, FTY720, prior to and during the first 17 days of M. tuberculosis challenge. This markedly reduced circulating T cells, but had no effect on the frequency of M. tuberculosis-specific CD4[SUP]+[/SUP] T[SUB]RMs[/SUB] in the lung parenchyma or their cytokine response to infection. Importantly, mice immunized with the rIAV vaccine were protected against M. tuberculosis infection even when circulating T cells were profoundly depleted by the treatment. Therefore, pulmonary immunization with the rIAV vaccine stimulates lung-resident CD4[SUP]+[/SUP] memory T cells that are associated with early protection against tuberculosis infection.
PMID: 30115996 DOI: 10.1038/s41385-018-0065-9