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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 15; pp. 8427 - 8432
• Main Authors: Stobie, Laura, Gurunathan, Sanjay, Prussin, Calman, Sacks, David L., Glaichenhaus, Nicolas, Wu, Chang-You, Seder, Robert A.
• 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: 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.160197797

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.