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

• Published in: The Journal of immunology (1950) Vol. 169; no. 1; pp. 63 - 67
• Main Authors: Peter, Katrin, Brunda, Michael J, Corradin, Giampietro
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.07.2002
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.1.63

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.