Andrew W Simonson, Joseph J Zeppa, Allison N Bucsan, Michael C Chao, Supriya Pokkali, Forrest Hopkins, Michael R Chase, Andrew J Vickers, Matthew S Sutton, Caylin G Winchell, Amy J Myers, Cassaundra L Ameel, Ryan J Kelly, Ben Krouse, Luke E Hood, Jiaxiang Li, Chelsea C Lehman, Megha Kamath, Jaime Tomko, Mark A Rodgers, Rachel Donlan, Harris Chishti, H Jacob Borish, Edwin Klein, Charles A Scanga, Sarah M Fortune, Philana Ling Lin, Pauline Maiello, Mario Roederer, Patricia A Darrah, Robert A Seder, JoAnne L Flynn
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引用次数: 0
Abstract
Tuberculosis (TB) is a major health burden worldwide despite widespread intradermal (ID) BCG vaccination in newborns. We previously demonstrated that changing the BCG route and dose from 5 × 105 CFUs ID to 5 × 107 CFUs i.v. resulted in prevention of Mycobacterium tuberculosis (Mtb) infection and TB disease in highly susceptible nonhuman primates. Identifying immune mechanisms protection following i.v. BCG will facilitate development of more effective vaccines against TB. Here, we depleted lymphocyte subsets prior to and during Mtb challenge in i.v. BCG-vaccinated macaques to identify those necessary for protection. Depletion of adaptive CD4 T cells, but not adaptive CD8αβ T cells, resulted in loss of protection with increased Mtb burdens and dissemination, indicating that CD4 T cells are critical to i.v. BCG-mediated protection. Depletion of unconventional CD8α-expressing lymphocytes (NK cells, innate T cells, and CD4+CD8α+ double-positive T cells) abrogated protection in most i.v. BCG-immunized macaques, supporting further investigation into which of these cell subsets contribute to protection after vaccination.
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Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field.
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