The Role of Antigen and IL-12 in Sustaining Th1 Memory Cells in vivo: IL-12 Is Required to Maintain Memory/Effector Th1 Cells Sufficient to Mediate Protection to an Infectious Parasite Challenge
IL-12 plays a central role in both the induction and magnitude of a primary Th1 response. A critical question in designing vaccines for diseases requiring Th1 immunity such as Mycobacterium tuberculosis and Leishmania major is the requirements to sustain memory/effector Th1 cells in vivo. This repor...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 15; pp. 8427 - 8432 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences of the United States of America
18.07.2000
National Acad Sciences National Academy of Sciences The National Academy of Sciences |
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Abstract | IL-12 plays a central role in both the induction and magnitude of a primary Th1 response. A critical question in designing vaccines for diseases requiring Th1 immunity such as Mycobacterium tuberculosis and Leishmania major is the requirements to sustain memory/effector Th1 cells in vivo. This report examines the role of IL-12 and antigen in sustaining Th1 responses sufficient for protective immunity to L. major after vaccination with LACK protein (LP) plus rIL-12 and LACK DNA. It shows that, after initial vaccination with LP plus rIL-12, supplemental boosting with either LP or rIL-12 is necessary but not sufficient to fully sustain long-term Th1 immunity. Moreover, endogenous IL-12 is also shown to be required for the induction, maintenance, and effector phase of the Th1 response after LACK DNA vaccination. Finally, IL-12 is required to sustain Th1 cells and control parasite growth in susceptible and resistant strains of mice during primary and secondary infection. Taken together, these data show that IL-12 is essential to sustain a sufficient number of memory/effector Th1 cells generated in vivo to mediate long-term protection to an intracellular pathogen. |
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AbstractList | IL-12 plays a central role in both the induction and magnitude of a primary Th1 response. A critical question in designing vaccines for diseases requiring Th1 immunity such as Mycobacterium tuberculosis and Leishmania major is the requirements to sustain memory/effector Th1 cells in vivo . This report examines the role of IL-12 and antigen in sustaining Th1 responses sufficient for protective immunity to L. major after vaccination with LACK protein (LP) plus rIL-12 and LACK DNA. It shows that, after initial vaccination with LP plus rIL-12, supplemental boosting with either LP or rIL-12 is necessary but not sufficient to fully sustain long-term Th1 immunity. Moreover, endogenous IL-12 is also shown to be required for the induction, maintenance, and effector phase of the Th1 response after LACK DNA vaccination. Finally, IL-12 is required to sustain Th1 cells and control parasite growth in susceptible and resistant strains of mice during primary and secondary infection. Taken together, these data show that IL-12 is essential to sustain a sufficient number of memory/effector Th1 cells generated in vivo to mediate long-term protection to an intracellular pathogen. IL-12 plays a central role in both the induction and magnitude of a primary Th1 response. A critical question in designing vaccines for diseases requiring Th1 immunity such as Mycobacterium tuberculosis and Leishmania major is the requirements to sustain memory/effector Th1 cells in vivo . This report examines the role of IL-12 and antigen in sustaining Th1 responses sufficient for protective immunity to L. major after vaccination with LACK protein (LP) plus rIL-12 and LACK DNA. It shows that, after initial vaccination with LP plus rIL-12, supplemental boosting with either LP or rIL-12 is necessary but not sufficient to fully sustain long-term Th1 immunity. Moreover, endogenous IL-12 is also shown to be required for the induction, maintenance, and effector phase of the Th1 response after LACK DNA vaccination. Finally, IL-12 is required to sustain Th1 cells and control parasite growth in susceptible and resistant strains of mice during primary and secondary infection. Taken together, these data show that IL-12 is essential to sustain a sufficient number of memory/effector Th1 cells generated in vivo to mediate long-term protection to an intracellular pathogen. This report examines the role of IL-12 and antigen in sustaining Th1 responses sufficient for protective immunity to L. major after vaccination with LACK protein (LP) plus rIL-12 and LACK DNA. It shows that, after initial vaccination with LP plus rIL-12, supplemental boosting with either LP or rIL-12 is necessary but not sufficient to fully sustain long-term Th1 immunity. |
Author | Sacks, David L. Seder, Robert A. Stobie, Laura Prussin, Calman Glaichenhaus, Nicolas Gurunathan, Sanjay Wu, Chang-You |
AuthorAffiliation | Clinical Immunology Section, Laboratory of Clinical Investigation, † Howard Hughes Medical Institute, ‡ Laboratory of Allergic Diseases, and § Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and ¶ Institut de Pharmacologie Moléculaire et Cellulaire, UPR411 Centre National de la Recherche Scientifique, 06560 Valbonne, France |
AuthorAffiliation_xml | – name: Clinical Immunology Section, Laboratory of Clinical Investigation, † Howard Hughes Medical Institute, ‡ Laboratory of Allergic Diseases, and § Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and ¶ Institut de Pharmacologie Moléculaire et Cellulaire, UPR411 Centre National de la Recherche Scientifique, 06560 Valbonne, France |
Author_xml | – sequence: 1 givenname: Laura surname: Stobie fullname: Stobie, Laura – sequence: 2 givenname: Sanjay surname: Gurunathan fullname: Gurunathan, Sanjay – sequence: 3 givenname: Calman surname: Prussin fullname: Prussin, Calman – sequence: 4 givenname: David L. surname: Sacks fullname: Sacks, David L. – sequence: 5 givenname: Nicolas surname: Glaichenhaus fullname: Glaichenhaus, Nicolas – sequence: 6 givenname: Chang-You surname: Wu fullname: Wu, Chang-You – sequence: 7 givenname: Robert A. surname: Seder fullname: Seder, Robert A. |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/10890924$$D View this record in MEDLINE/PubMed |
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Snippet | IL-12 plays a central role in both the induction and magnitude of a primary Th1 response. A critical question in designing vaccines for diseases requiring Th1... This report examines the role of IL-12 and antigen in sustaining Th1 responses sufficient for protective immunity to L. major after vaccination with LACK... |
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StartPage | 8427 |
SubjectTerms | Animals Antigens Antigens, Protozoan - genetics Antigens, Protozoan - immunology Biological Sciences CD4 Antigens - immunology Cells Cellular immunity DNA Female Immunity Immunity, Innate - immunology Immunization Immunologic Memory - immunology Immunology Infections Interleukin-12 - genetics Interleukin-12 - immunology LACK antigen Leishmania major Leishmania major - immunology Leishmaniasis, Cutaneous - immunology Leishmaniasis, Cutaneous - prevention & control Lymph nodes Memory Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mycobacterium tuberculosis Parasites Protozoan Proteins - genetics Protozoan Proteins - immunology Protozoan Vaccines - genetics Protozoan Vaccines - immunology T lymphocytes Th1 Cells - immunology Time Factors Vaccination Vaccines Vaccines, DNA - genetics Vaccines, DNA - immunology |
Title | The Role of Antigen and IL-12 in Sustaining Th1 Memory Cells in vivo: IL-12 Is Required to Maintain Memory/Effector Th1 Cells Sufficient to Mediate Protection to an Infectious Parasite Challenge |
URI | https://www.jstor.org/stable/122917 http://www.pnas.org/content/97/15/8427.abstract https://www.ncbi.nlm.nih.gov/pubmed/10890924 https://www.proquest.com/docview/201397352/abstract/ https://search.proquest.com/docview/17677498 https://search.proquest.com/docview/71260729 https://pubmed.ncbi.nlm.nih.gov/PMC26964 |
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