Mycobacteria-specific CD4+IFN-γ+ cell expresses naïve-surface markers and confers superior protection against tuberculosis infection compared to central and effector memory CD4+ T cell subsets

• Published in: bioRxiv
• Main Authors: Yuan, Jinyun, Tenant, Janice, Pacatte, Thomas, Eickhoff, Christopher, Blazevic, Azra, Hoft, Daniel F., Chatterjee, Soumya
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Laboratory 16.08.2018
• Edition: 1.3
• Subjects: Immunology; CD4+memory; Tuberculosis vaccine; tuberculosis immunology; T cell memory; Cell-mediated immunity to tuberculosis
• ISSN: 2692-8205
• DOI: 10.1101/384784

Failure of the most recent tuberculosis (TB) vaccine trial to boost BCG mediated anti-TB immunity despite highly durable Th1-specific central (TCM) and effector (TEM) memory cell responses, highlights the importance of identifying optimal T cell targets for protective vaccines. Here we describe a novel, Mycobacterium tuberculosis (Mtb)-specific IFN-γ+CD4+ T cell population expressing surface markers characteristic of naïve T cells (TNLM), that were induced in both human (CD45RA+CCR7+CD27+CD95-) and murine (CD62L+CD44-Sca-1+CD122-) systems in response to mycobacteria. In BCG vaccinated subjects and those with latent TB infection, TNLM cells, compared to bonafide naïve CD4+ T cells were identified by absence of CD95 expression and had increased expression CCR7 and CD27, the activation markers T-bet, CD69 and PD-1 and the survival marker CD74. Increased TNLM frequencies were noted in the lung and spleen of wild type C57BL6 mice at 2 weeks after infection with Mtb, and progressively decreased at later time points, a pattern not seen in TNF-α+CD4+ T cells expressing naïve cell surface markers. Importantly, adoptive transfer of highly purified TNLM from vaccinated ESAT-61-20-specific TCR transgenic mice conferred superior protection against Mtb infection in Rag-/- mice when compared with total meory populations (central and effector memory cells). Thus, TNLM cells may represent a memory T cell population that if optimally targeted may significantly improve future TB vaccine responses.