IL-12 administration leads to a transient depletion of T cells, B cells, and APCs and concomitant abrogation of the HLA-A2.1-restricted CTL response in transgenic mice.
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.
Peter
Katrin
K
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Brunda
Michael J
MJ
Corradin
Giampietro
G
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D015789:HLA-A2 Antigen / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000008:administration & dosage*; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D009842:Oligopeptides; D011994:Recombinant Proteins; D018664:Interleukin-12