Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T Cells

• Published in: The Journal of immunology (1950) 2000-07, Vol.165 (2), p.915-924
• Main Authors: Gurunathan, Sanjay, Stobie, Laura, Prussin, Calmin, Sacks, David L, Glaichenhaus, Nicolas, Fowell, Deborah J, Locksley, Richard M, Chang, John T, Wu, Chang-You, Seder, Robert A
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Protozoan - administration & dosage; Antigens, Protozoan - immunology; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8 Antigens - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Division - immunology; Cells, Cultured; DNA, Protozoan - administration & dosage; DNA, Protozoan - immunology; Genes, T-Cell Receptor beta; Immune Sera - administration & dosage; Immunity, Cellular; Injections, Subcutaneous; Interferon-gamma - biosynthesis; Interleukin-12 - administration & dosage; Interleukin-12 - antagonists & inhibitors; Interleukin-12 - biosynthesis; Interleukin-12 - metabolism; Leishmania major - enzymology; Leishmania major - genetics; Leishmania major - immunology; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - prevention & control; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Transgenic; Protein Kinase C - metabolism; Protozoan Proteins - administration & dosage; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Receptors, Interleukin - antagonists & inhibitors; Receptors, Interleukin - biosynthesis; Receptors, Interleukin-12; Th1 Cells - immunology; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.2.915

Protective immunity against Leishmania major generated by DNA encoding the LACK (Leishmania homologue of receptor for activated C kinase) Ag has been shown to be more durable than vaccination with LACK protein plus IL-12. One mechanism to account for this may be the selective ability of DNA vaccination to induce CD8+ IFN-gamma-producing T cells. In this regard, we previously reported that depletion of CD8+ T cells in LACK DNA-vaccinated mice abrogated protection when infectious challenge was done 2 wk postvaccination. In this study, we extend these findings to study the mechanism by which CD8+ T cells induced by LACK DNA vaccination mediate both short- and long-term protective immunity against L. major. Mice vaccinated with LACK DNA and depleted of CD8+ T cells at the time of vaccination or infection were unable to control infection when challenge was done 2 or 12 wk postvaccination. Remarkably, it was noted that depletion of CD8+ T cells in LACK DNA-vaccinated mice was associated with a striking decrease in the frequency of LACK-specific CD4+ IFN-gamma-producing T cells both before and after infection. Moreover, data are presented to suggest a mechanism by which CD8+ T cells exert this regulatory role. Taken together, these data provide additional insight into how Th1 cells are generated and sustained in vivo and suggest a potentially novel immunoregulatory role for CD8+ T cells following DNA vaccination.