Immunity & infection

Poster

Ratio Between Hbha- and esat-6-induced Polycytotoxic cd4+ T Cells, a New Biomarker for Ltbi

Wednesday, June 14
6:15 PM - 7:45 PM

Tuberculosis (TB) remains the leading cause of death from a curable infection with 1.4 million TB deaths reported in 2015. Mycobacterium tuberculosis (Mtb) is so infrequently cleared from its host that an estimated one-third of the world population is latently infected (LTBI), most often for life. Five to 10% of LTBI individuals will, at some point, convert to active TB (aTB). Finding a biomarker that can discriminate LTBI from aTB is absolutely essential if the WHO's End TB Strategy target of a 90% reduction in TB deaths by 2030 is to be achieved.


We developed a 7 day in vitro PBMC stimulation assay in which we used lymphoblast formation, measured as FSC/SSC changes observed by flow cytometry, as a measure for T lymphocyte activation and proliferation. Such 7 days stimulation of PBMC from Mtb infected individuals (n=27), with the mycobacterial antigen heparin-binding hemagglutinin (HBHA) induced degranulation of CD4+ lymphoblasts, measured by the surface expression of CD107a, whereas PBMC from healthy, uninfected individuals (n=10) did not (p < 0.001). Furthermore, we demonstrated that HBHA stimulation induced proliferation of CD4+Polycytotoxic T cells (PCTL), releasing granulysin, granzymes, perforin and IFN-gamma simultaneously, in LTBI individuals (n=9), while significantly less PCTL proliferation was observed in aTB individuals (n=8). Conversely, the 6 kDa early-secretory-antigenic-target (ESAT6) induced PCTL proliferation in aTB individuals but not in LTBI. In fact, the ratio of PCTL induced by HBHA to PCTL induced by ESAT6 allows for the discrimination of LTBI and aTB individuals (p < 0.001) , representing, thus, a novel LTBI biomarker.

Laetitia Aerts

Laboratory of Vaccinology and Mucosal Immunity, Multinational FOCIS Center of Excellence, Université Libre de Bruxelles, Brussels, Belgium

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    Elodie Selis

    Laboratory of Vaccinology and Mucosal Immunity, Multinational FOCIS Center of Excellence, Université Libre de Bruxelles, Brussels, Belgium

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      Véronique Corbière

      Laboratory of Vaccinology and Mucosal Immunity, Multinational FOCIS Center of Excellence, Université Libre de Bruxelles, Brussels, Belgium

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        Kaat Smits

        Laboratory of Vaccinology and Mucosal Immunity, Multinational FOCIS Center of Excellence, Université Libre de Bruxelles, Brussels, Belgium

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          Anne Van praet

          Laboratory of Vaccinology and Mucosal Immunity, Multinational FOCIS Center of Excellence, Université Libre de Bruxelles, Brussels, Belgium

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            Myriam Libin

            Laboratory of Vaccinology and Mucosal Immunity, Multinational FOCIS Center of Excellence, Université Libre de Bruxelles, Brussels, Belgium

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              Emmanuelle Petit

              U1019—UMR8204-CIIL-, Center for Infection and Immunity of Lille, Lille, France and Institut Pasteur de Lille, Lille, France

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                Mahavir Singh

                Lionex Diagnostics & Therapeutics, Braunschweig, Germany

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                  Camille Locht

                  U1019—UMR8204-CIIL-, Center for Infection and Immunity of Lille, Lille, France and Institut Pasteur de Lille, Lille, France

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                    Violette Dirix

                    Laboratory of Vaccinology and Mucosal Immunity, Multinational FOCIS Center of Excellence, Université Libre de Bruxelles, Brussels, Belgium

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                      Françoise Mascart

                      Laboratory of Vaccinology and Mucosal Immunity, Multinational FOCIS Center of Excellence, Université Libre de Bruxelles, Brussels, Belgium

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                        Ratio Between Hbha- and esat-6-induced Polycytotoxic cd4+ T Cells, a New Biomarker for Ltbi



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