BCG-reactive CD8 T cells after Revaccination of Latently <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>) Infected Adults are Predominantly CD26<sup>+</sup>CD161<sup>+</sup> MAIT cells — ASN Events
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  2. Session 9 - Microbial Immunity
  3. BCG-reactive CD8 T cells after Revaccination of Latently Mycobacterium tuberculosis (M.tb) Infected Adults are Predominantly CD26+CD161+ MAIT cells

BCG-reactive CD8 T cells after Revaccination of Latently Mycobacterium tuberculosis (M.tb) Infected Adults are Predominantly CD26+CD161+ MAIT cells (#69)

Sara Suliman 1 , Hennie Geldenhuys 1 , John L Johnson 2 , Jane E Hughes 1 , Erica Smit 1 , Asma Toefy 1 , Christiaan Hopley 1 , Bernadette Pienaar 1 , Phalkun Chheng 2 , Willem Hanekom 1 , W H Boom 2 , Mark Hatherill 1 , Thomas J Scriba 1
  1. South African TB Vaccine Initiative, Observatory, Cape Town, WESTERN CAPE, South Africa
  2. Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH, USA

Introduction:

One third of the global population is estimated to be latently Mycobacterium tuberculosis (M.tb) infected (LTBI), and hence, at risk of TB disease. These LTBI individuals may benefit from vaccination. We performed a phase I trial of Bacille Calmette-Guerin (BCG) revaccination to study induced immune responses. We hypothesized that BCG revaccination would boost frequencies of MR1-restricted, BCG-reactive mucosal associated invariant T (MAIT) cells.

Methods:

Tuberculin skin test (TST) positive, HIV-seronegative, healthy South African adults, who received BCG at birth, were treated with isozianid for 6 months and then revaccinated with BCG SSI (Statens Serum Institut, Copenhagen). Whole blood from multiple time-points pre- and post-vaccination was stimulated with BCG or ESAT-6/CFP-10 peptide pools and immune responses were measured by intracellular cytokine staining using flow cytometry.

Results:

All participants had BCG-reactive CD8 T cells expressing IFN-γ and/or TNF-α before BCG-revaccination.  BCG transiently boosted the frequencies of these CD8 responses, which had returned to pre-vaccination levels by 1 year after vaccination. We then investigated expression of CD161 and CD26, lineage markers of MAIT cells, by these cytokine-producing BCG-reactive CD8 T cells. CD26+CD161+ MAIT cells comprised the majority of BCG-induced IFN-γ-expressing CD8 T-cells. By contrast, CD26-CD161- “conventional” CD8 T cells comprised the majority of ESAT-6/CFP-10-induced IFNγ responses.   

Discussion:

Our results suggest that the whole cell BCG vaccine induced BCG-reactive, cytokine expressing CD8 MAIT cells, even in persons from a setting endemic for TB, who were highly pre-sensitized to mycobacteria. Surprisingly, these MAIT cells comprised the majority of BCG-reactive CD8 T cells, which were previously thought to be peptide-antigen specific conventional T cells. Experiments to determine whether these MAIT cell responses are MR1-dependent, and to what degree they depend on cytokine expression by other BCG-responsive cells are underway.