Poster Presentation CD1-MR1 2024

MAIT cell activation and memory phenotypes in highly exposed healthcare workers with resistance to Mycobacterium tuberculosis infection (#211)

Avuyonke Balfour 1 , Nomawethu Masina 1 , Abulele Bekiswa 1 , Rene Goliath 1 , Katalin A Wilkinson 2 , Charlotte Schutz 1 , Graeme Meintjes 1 , Muki Shey 1
  1. University of Cape Town, Cape Town, WESTERN CAPE, South Africa
  2. The Francis Crick Institute, London, United Kingdom

Introduction

Evidence exists that some individuals possibly resist Mycobacterium tuberculosis (Mtb) infection despite sustained exposure (resisters), but the protective mechanisms involved are not yet fully understood. Mucosal-associated invariant T (MAIT) cells may contribute to the initial clearance of Mtb infection because they can be rapidly activated with or without antigen recognition. This study investigated the activation and memory phenotypes of MAIT cells in resisters.

 Methods

HIV-uninfected healthcare workers who had worked in TB health care facilities for 5years or more were screened for Mtb sensitization using the interferon-gamma release assay (IGRA) and the tuberculin skin test (TST). Individuals with the phenotype of ‘Extreme resisters’ (TST=0mm and IGRA<0.2 IU/mL; n=25) and ‘extreme latent TB infection’, LTBI (TST³15mm and IGRA³1 IU/mL; n=15) were enrolled, blood was collected and peripheral blood mononuclear cells (PBMCs) isolated. PBMCs were stimulated with live H37Rv Mtb strain for 18 hours. MAIT cells were identified using the MR1-tetramer and MAIT cell activation (expression of HLA-DR/CD38/CD27) and memory phenotypes (expression of CD27/CD45RA/CCR7) were analysed using flow cytometry.

Results

Similar frequencies of MAIT cells between resisters and LTBI were observed in unstimulated samples. Resisters had higher unstimulated frequencies of MAIT cells expressing HLA-DR (Median[IQR]: 21.30[16.70-27.20] vs 13.50[9.49-15.10]; p=0.018) and CD27 (82.80[76.30-89.70] vs 77.10[62.50-84.90]; p=0.038), but similar unstimulated frequencies for total CD38 and all markers upon stimulation with Mtb. In co-expression analyses of these markers with stimulation, there were higher frequencies of MAIT cells expressing CD38 alone in LTBI compared with resisters (7.95[2.91-13.78] vs 0[0-0]; p=0.0001). Frequencies of effector memory MAIT cells (CD45RA-CCR7-CD27-) were higher in LTBI compared with resisters (20[13.80-27.40] vs 13.00[8.18-17.30]; p=0.010). All other memory subsets were similar between the two groups.

Conclusion

Resistance to Mtb infection is associated with higher basal MAIT cell activation. Further analyses are underway exploring MAIT cells in resistance to Mtb infection.