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J Immunol. 2019 Jan 15;202(2):421-427. doi: 10.4049/jimmunol.1800840. Epub 2018 Dec 17.

HBHA-Induced Polycytotoxic CD4+ T Lymphocytes Are Associated with the Control of Mycobacterium tuberculosis Infection in Humans.

Author information

1
Laboratoire de Vaccinologie et d'Immunologie Mucosale, Université Libre de Bruxelles, 1070 Brussels, Belgium.
2
Département de Maladies Infectieuses, Centre Hospitalier Universitaire Saint-Pierre, Université Libre de Bruxelles, 1000 Brussels, Belgium.
3
INSERM, U1019, F-59019 Lille, France.
4
CNRS, UMR8204, F-59019 Lille, France.
5
Université de Lille, F-59019 Lille, France.
6
Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France.
7
Lionex Diagnostics and Therapeutics, D-38023 Braunschweig, Germany; and.
8
Laboratoire de Vaccinologie et d'Immunologie Mucosale, Université Libre de Bruxelles, 1070 Brussels, Belgium; fmascart@ulb.ac.be.
9
Clinique d'Immunobiologie, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium.

Abstract

Heparin-binding hemagglutinin (HBHA), a surface protein of Mycobacterium tuberculosis, is an attractive vaccine candidate and marker of protective immunity against tuberculosis, although the mechanisms underlying this protective immunity are not fully understood. Comparisons of the immune responses of latently M. tuberculosis-infected (LTBI) subjects to those of patients with active tuberculosis (aTB) may help to identify surrogate markers of protection, as LTBI subjects are most often lifelong protected against the disease. HBHA was shown to induce strong Th1 responses and cytotoxic CD8+ responses in LTBI subjects, but additional mechanisms of control of M. tuberculosis infection remain to be identified. In this study, using HBHA-induced blast formation as a readout of specific T lymphocyte activation, we report the presence in M. tuberculosis-infected subjects of HBHA-induced CD4+ T cell blasts that degranulate, as measured by surface capture of CD107a. This suggests the induction by HBHA of a CD4+ T cell subset with cytolytic function, and as nearly half of these cells also contained IFN-γ, they had both Th1 and cytotoxic characteristics. We further identified a CD4+ T lymphocyte subset producing IFN-γ together with a combination of mediators of cytotoxicity, i.e., perforin, granzymes, and granulysin, and we called them polycytotoxic CD4+ T lymphocytes. Interestingly, whereas purified protein derivative induced such cells in both LTBI subjects and patients with aTB, HBHA-specific polycytotoxic CD4+ T lymphocytes were detected in LTBI subjects and not in patients with pulmonary aTB. To our knowledge, we thus identified a new HBHA-induced CD4+ T cell subset that may contribute to the control of M. tuberculosis infection.

PMID:
30559320
DOI:
10.4049/jimmunol.1800840

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