Requirements for the maintenance of Th1 immunity in vivo following DNA vaccination: a potential immunoregulatory role for CD8+ T cells

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 vaccinat...

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Veröffentlicht in:	The Journal of immunology (1950) Jg. 165; H. 2; S. 915
Hauptverfasser:	Gurunathan, S, Stobie, L, Prussin, C, Sacks, D L, Glaichenhaus, N, Iwasaki, A, Fowell, D J, Locksley, R M, Chang, J T, Wu, C Y, Seder, R A
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 15.07.2000
Schlagworte:	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
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-1767
DOI:	10.4049/jimmunol.165.2.915