Abstract
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.
MeSH terms
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Animals
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Antigens, Protozoan / administration & dosage
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Antigens, Protozoan / immunology
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CD4 Lymphocyte Count
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8 Antigens / immunology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Division / immunology
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Cells, Cultured
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DNA, Protozoan / administration & dosage
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DNA, Protozoan / immunology
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Genes, T-Cell Receptor beta
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Immune Sera / administration & dosage
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Immunity, Cellular
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Injections, Subcutaneous
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Interferon-gamma / biosynthesis
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Interleukin-12 / administration & dosage
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Interleukin-12 / antagonists & inhibitors
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Interleukin-12 / biosynthesis
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Interleukin-12 / metabolism
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Leishmania major / enzymology
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Leishmania major / genetics
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Leishmania major / immunology
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Leishmaniasis, Cutaneous / immunology
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Leishmaniasis, Cutaneous / prevention & control
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Lymph Nodes / cytology
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Lymph Nodes / immunology
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Lymphocyte Activation
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Protein Kinase C / metabolism
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Protozoan Proteins / administration & dosage
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Protozoan Proteins / genetics
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Protozoan Proteins / immunology
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Receptors, Interleukin / antagonists & inhibitors
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Receptors, Interleukin / biosynthesis
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Receptors, Interleukin-12
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Th1 Cells / immunology*
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Vaccines, DNA / administration & dosage*
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Vaccines, DNA / immunology*
Substances
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Antigens, Protozoan
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CD8 Antigens
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DNA, Protozoan
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Immune Sera
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Protozoan Proteins
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Receptors, Interleukin
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Receptors, Interleukin-12
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Vaccines, DNA
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LACK antigen, Leishmania
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Interleukin-12
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Interferon-gamma
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Protein Kinase C