Protection against disseminated disease following reinfection with Mycobacterium tuberculosis requires CD8+ lymphocytes
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 CD8α 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, CD8α 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.
Authors
- Forrest F. Hopkins (ORCID: https://orcid.org/0000-0002-3801-4673)
- Charles A. Scanga (ORCID: https://orcid.org/0000-0003-3654-5603)
- Ryan J. Kelly (ORCID: https://orcid.org/0009-0008-7055-4689)
- Michael C. Chao (ORCID: https://orcid.org/0000-0003-3158-7337)
- Henry Jacob Borish (ORCID: https://orcid.org/0000-0002-9220-673X)
- Philana Ling Lin (ORCID: https://orcid.org/0000-0001-5169-3714)
- Mark Rodgers (ORCID: https://orcid.org/0000-0001-9800-3362)
- Edwin C. Klein (ORCID: https://orcid.org/0009-0002-4328-5344)
- Jaime A. Tomko (ORCID: https://orcid.org/0000-0002-9308-4957)
- Jennifer Schober (ORCID: https://orcid.org/0000-0001-7888-6671)
- Cassaundra L. Ameel (ORCID: https://orcid.org/0009-0000-0330-1587)
- Pauline A Maiello (ORCID: https://orcid.org/0000-0002-5188-8420)
- Feng Shan (ORCID: https://orcid.org/0000-0003-3660-8475)
- Harris B. Chishti (ORCID: https://orcid.org/0009-0009-0880-0532)
- JoAnne L. Flynn (ORCID: https://orcid.org/0000-0001-7874-8981)
- Andrew W. Simonson (ORCID: https://orcid.org/0000-0003-4789-3873)
- Alex K. Shalek (ORCID: https://orcid.org/0000-0001-5670-8778)
- Sarah M. Fortune (ORCID: https://orcid.org/0000-0001-7565-9975)
- Michael R. Chase (ORCID: https://orcid.org/0000-0002-9789-0542)
- Kara B. Kracinovsky
- Alexander A. Smith
- Luke E Hood (ORCID: https://orcid.org/0009-0006-9633-7290)
- E Grace Bothwell
- Marshall Malin
- Alanna Callendrello
Institutions
- Tufts University (US)
- Harvard University (US)
- University of Pittsburgh (US)
- Children's Hospital of Pittsburgh (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-11-03
- DOI
- https://doi.org/10.64898/2026.10.29.762796
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- preprint