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 |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 To whom reprint requests should be addressed. E-mail: rseder@nih.gov. Edited by Anthony S. Fauci, National Institutes of Health, Bethesda, MD, and approved June 7, 2000 |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.160197797 |