Protection against disseminated disease following reinfection with Mycobacterium tuberculosis requires CD8+ lymphocytes
- 11Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine; Pittsburgh, PA, USA. 2Center for Vaccine Research, University o
Abstract
Concomitant immunity is protective adaptive immunity conferred by pre-existing infection against subsequent exposures. This phenomenon is effective in the context of human tuberculosis (TB) and has been successfully recapitulated in non-human primates (NHPs). We previously demonstrated that depletion of CD4 T cells prior to secondary challenge with Mycobacterium tuberculosis (Mtb) only partially abrogated protection, implicating a critical role for additional cell types. Here, we describe the effects of depleting CD8 expressing cells in this model. CD4+ T cells in the airway were unable to compensate for lost cytotoxicity due to CD8 depletion. Contrary to the results of CD4 depletion, CD8 depleted animals exhibited a unique inability to limit Mtb dissemination, with significant lymph node involvement despite a short 4-week infection. These data suggest that concomitant immunity relies on non-redundant roles played by CD8+ lymphocytes. Thus, future vaccines should be designed to induce effective responses by both CD4+ and CD8+ populations to maximize efficacy.
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BibTeX
@misc{simonson2026protection,
title = {{Protection against disseminated disease following reinfection with Mycobacterium tuberculosis requires CD8+ lymphocytes}},
author = {A. W. Simonson and M. C. Chao and E. G. Bothwell and F. Shan and M. A. Rodgers and L. E. Hood and F. Hopkins and M. R. Chase and A. Callendrello and A. A. Smith and R. J. Kelly and C. L. Ameel and E. Klein and J. Schober and K. Kracinovsky and J. A. Tomko and H. Chishti and M. Malin and H. J. Borish and P. Maiello and C. A. Scanga and P. L. Lin and A. K. Shalek and S. M. Fortune and J. L. Flynn},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762796},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762796v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Protection against disseminated disease following reinfection with Mycobacterium tuberculosis requires CD8+ lymphocytes
AU - A. W. Simonson
AU - M. C. Chao
AU - E. G. Bothwell
AU - F. Shan
AU - M. A. Rodgers
AU - L. E. Hood
AU - F. Hopkins
AU - M. R. Chase
AU - A. Callendrello
AU - A. A. Smith
AU - R. J. Kelly
AU - C. L. Ameel
AU - E. Klein
AU - J. Schober
AU - K. Kracinovsky
AU - J. A. Tomko
AU - H. Chishti
AU - M. Malin
AU - H. J. Borish
AU - P. Maiello
AU - C. A. Scanga
AU - P. L. Lin
AU - A. K. Shalek
AU - S. M. Fortune
AU - J. L. Flynn
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762796
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762796v1
AB - Concomitant immunity is protective adaptive immunity conferred by pre-existing infection against subsequent exposures. This phenomenon is effective in the context of human tuberculosis (TB) and has been successfully recapitulated in non-human primates (NHPs). We previously demonstrated that depletion of CD4 T cells prior to secondary challenge with Mycobacterium tuberculosis (Mtb) only partially abrogated protection, implicating a critical role for additional cell types. Here, we describe the effects of depleting CD8 expressing cells in this model. CD4+ T cells in the airway were unable to compensate for lost cytotoxicity due to CD8 depletion. Contrary to the results of CD4 depletion, CD8 depleted animals exhibited a unique inability to limit Mtb dissemination, with significant lymph node involvement despite a short 4-week infection. These data suggest that concomitant immunity relies on non-redundant roles played by CD8+ lymphocytes. Thus, future vaccines should be designed to induce effective responses by both CD4+ and CD8+ populations to maximize efficacy.
ER -