Effector Functions of Heparin-Binding Hemagglutinin–Specific CD8+ T Lymphocytes in Latent Human Tuberculosis
BackgroundMost 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 defini...
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| Published in | The Journal of infectious diseases Vol. 192; no. 2; pp. 226 - 232 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Chicago, IL
The University of Chicago Press
15.07.2005
University of Chicago Press |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0022-1899 1537-6613 1537-6613 |
| DOI | 10.1086/430930 |
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| Abstract | BackgroundMost 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)–γ 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 ResultsHBHA-specific CD8+ T lymphocytes expressed memory cell markers and synthesized HBHA-specific IFN-γ. 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-γ–producing CD8+ T lymphocytes ConclusionDuring 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 |
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| AbstractList | 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)-γ 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-γ. They also restricted mycobacterial growth and expressed cytotoxicity by a granule-dependent mechanism. This activity was associated with the intracellular expression of HBHA-induced perform. Surprisingly, the perforin-producing CD8⁺ T lymphocytes were distinct from the IFN-γ-producing CD8⁺ T lymphocytes. Conclusion. 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. 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.BACKGROUNDMost 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.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.RESULTSHBHA-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.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.CONCLUSIONDuring 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. 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. 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. 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. BackgroundMost 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)–γ 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 ResultsHBHA-specific CD8+ T lymphocytes expressed memory cell markers and synthesized HBHA-specific IFN-γ. 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-γ–producing CD8+ T lymphocytes ConclusionDuring 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 BackgroundMost 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)-γ 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 ResultsHBHA-specific CD8+ T lymphocytes expressed memory cell markers and synthesized HBHA-specific IFN-γ. 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-γ-producing CD8+ T lymphocytes ConclusionDuring 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 |
| Author | Temmerman, Stéphane T. Mascart, Françoise Place, Sammy Debrie, Anne-Sophie Locht, Camille |
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| Keywords | Human Infection Tuberculosis Microbiology Hemagglutinin T-Lymphocyte Bacteriosis Anticoagulant Mycobacterial infection Heparin |
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| Snippet | BackgroundMost individuals infected with Mycobacterium tuberculosis do not develop tuberculosis (TB) and can be regarded as being protected by an appropriate... Background. Most individuals infected with Mycobacterium tuberculosis do not develop tuberculosis (TB) and can be regarded as being protected by an appropriate... Most individuals infected with Mycobacterium tuberculosis do not develop tuberculosis (TB) and can be regarded as being protected by an appropriate immune... |
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| SubjectTerms | Antigens Bacteria Bacterial diseases Biological and medical sciences CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - microbiology Cell Survival Cytotoxicity Fundamental and applied biological sciences. Psychology Hemagglutinins - physiology Human bacterial diseases Humans Immunity Infections Infectious diseases Latent tuberculosis Lectins Macrophages - microbiology Medical sciences Membrane Glycoproteins - biosynthesis Microbiology Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Perforin Pore Forming Cytotoxic Proteins T lymphocytes Tuberculosis Tuberculosis - immunology Tuberculosis - microbiology Tuberculosis and atypical mycobacterial infections Tuberculosis vaccine Vaccination |
| Title | Effector Functions of Heparin-Binding Hemagglutinin–Specific CD8+ T Lymphocytes in Latent Human Tuberculosis |
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