Effector functions of heparin-binding hemagglutinin-specific CD8+ T lymphocytes in latent human tuberculosis.
BACKGROUND
Most individuals infected with Mycobacterium tuberculosis do not develop tuberculosis (TB) and can be regarded as being protected by an appropriate immune response to the infection. The characterization of the immune responses of individuals with latent TB may thus be helpful in the definition of correlates of protection and the development of new vaccine strategies. The highly protective antigen heparin-binding hemagglutinin (HBHA) induces strong interferon (IFN)- gamma responses during latent, but not active, TB. Because of the recently recognized importance of CD8(+) T lymphocytes in anti-TB immunity, we characterized the CD8(+) T lymphocyte responses to HBHA in subjects with latent TB.


RESULTS
HBHA-specific CD8(+) T lymphocytes expressed memory cell markers and synthesized HBHA-specific IFN- gamma . They also restricted mycobacterial growth and expressed cytotoxicity by a granule-dependent mechanism. This activity was associated with the intracellular expression of HBHA-induced perforin. Surprisingly, the perforin-producing CD8(+) T lymphocytes were distinct from the IFN- gamma -producing CD8(+) T lymphocytes.


CONCLUSIONS
During latent TB, the HBHA-specific CD8(+) T lymphocyte population expresses all 3 effector functions associated with CD8(+) T lymphocyte-mediated protective immune mechanisms, which supports the notion that HBHA may be protective in humans and suggests that markers of HBHA-specific CD8(+) T lymphocyte responses may be useful in the monitoring of protection.
Temmerman
Stéphane T
ST
Laboratory of Vaccinology and Mucosal Immunity, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
Place
Sammy
S
Debrie
Anne-Sophie
AS
Locht
Camille
C
Mascart
Françoise
F
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D002470:Cell Survival; D006388:Hemagglutinins / Q000502:physiology*; D006801:Humans; D037102:Lectins; D008264:Macrophages / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
D006388:Hemagglutinins; D037102:Lectins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; C104578:heparin-binding hemagglutinin; D054353:Perforin