Abstract
The injection of a mixture of bona fide T cell epitopes can lead to the occurrence of immunodominance, meaning that the immune response is focused on the recognition of a single epitope or a small portion of the epitopes injected. We have previously demonstrated that the administration of rIL-12 can counteract immunodominance in BALB/c mice. In this study, we show that the administration of rIL-12 to HLA-A2.1 transgenic mice (A2k(b) mice) abrogates specifically the immune response against HLA-A2.1-restricted HIV epitopes in the spleen. This lack of immune response is most probably due to a transient depletion of B cells, T cells, macrophages, and dendritic cells in this organ. Therefore, our study explains the mechanism of immunosuppression by rIL-12 in vivo.
MeSH terms
-
AIDS Vaccines / administration & dosage
-
AIDS Vaccines / immunology
-
Animals
-
Antigen-Presenting Cells / immunology*
-
B-Lymphocytes / immunology*
-
Cells, Cultured
-
Cytotoxicity, Immunologic / genetics*
-
Down-Regulation / genetics
-
Down-Regulation / immunology
-
Epitopes, T-Lymphocyte / genetics
-
Epitopes, T-Lymphocyte / immunology
-
Female
-
H-2 Antigens / genetics
-
HLA-A2 Antigen / biosynthesis
-
HLA-A2 Antigen / genetics*
-
HLA-A2 Antigen / immunology
-
Immunodominant Epitopes / genetics
-
Immunodominant Epitopes / immunology
-
Injections, Intraperitoneal
-
Interleukin-12 / administration & dosage*
-
Lymphocyte Depletion / methods*
-
Male
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Mice, Transgenic
-
Oligopeptides / administration & dosage
-
Oligopeptides / immunology
-
Recombinant Proteins / administration & dosage
-
Spleen / cytology
-
Spleen / immunology
-
Spleen / metabolism
-
T-Lymphocytes / immunology*
Substances
-
AIDS Vaccines
-
Epitopes, T-Lymphocyte
-
H-2 Antigens
-
H-2Kb protein, mouse
-
HLA-A2 Antigen
-
Immunodominant Epitopes
-
Oligopeptides
-
Recombinant Proteins
-
Interleukin-12