Heparin-Binding Hemagglutinin Induces IFN-γ+ IL-2+ IL-17+ Multifunctional CD4+ T Cells during Latent but Not Active Tuberculosis Disease

The mycobacterial heparin-binding hemagglutinin (HBHA) protein induces a potent gamma interferon (IFN-gamma) response in latent tuberculosis (TB) infection and is a candidate vaccine and diagnostic antigen. We have assessed HBHA-specific intracellular IFN-gamma, interleukin-2 (IL-2), and IL-17 production by CD4(+) T cells in TB cases and household contacts (HHCs) as well as the level of secreted IFN-gamma in whole-blood culture supernatant. HHCs were further classified as tuberculin skin test (TST) positive or negative, and the group was also divided as HIV positive or negative. Our study revealed that HBHA induces multifunctional IFN-gamma-, IL-2-, and IL-17-coexpressing CD4(+) T cells in HHCs but not in active TB cases; however, IFN-gamma levels in culture supernatant did not differ between participant groups. Further studies are needed to completely understand how HBHA induces immune responses in different disease groups.