Department of Microbiology and Physiological Systems; Division of Infectious Disease and Immunology, Department of Medicine; Graduate School of Biomedical Sciences
Bacterial Infections and Mycoses | Immunoprophylaxis and Therapy
Immunological memory is the key biological process that makes vaccines possible. Although tuberculosis vaccines elicit protective immunity in animals, few provide durable protection. To understand why protection is transient, we evaluated the ability of memory CD4+ T cells to expand, differentiate, and control Mycobacterium tuberculosis. Both naive and memory CD4+ T cells initially proliferated exponentially, and the accumulation of memory T cells in the lung correlated with early bacterial control. However, later during infection, memory CD4+ T cell proliferation was curtailed and no protection was observed. We show that memory CD4+ T cells are first activated in the LN and their recruitment to the lung attenuates bacterial growth. However, their interaction with Mtb-infected macrophages does not promote continued proliferation. We conclude that a lack of sustained expansion by memory-derived T cells in the lung limits the durability of their protection, linking their slower expansion with transient protection in vaccinated mice.
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Copyright: © 2017 Carpenter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS Pathog. 2017 Nov 27;13(11):e1006704. doi: 10.1371/journal.ppat.1006704. eCollection 2017 Nov. Link to article on publisher's site
Carpenter SM, Yang JD, Lee J, Barreira-Silva P, Behar SM. (2017). Vaccine-elicited memory CD4+ T cell expansion is impaired in the lungs during tuberculosis. Open Access Articles. https://doi.org/10.1371/journal.ppat.1006704. Retrieved from https://escholarship.umassmed.edu/oapubs/3302
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