IFN-alpha secretion by type 2 predendritic cells up-regulates MHC class I in the HIV-1-infected thymus.
The ability of HIV-1 to evade the host immune response leads to the establishment of chronic infection. HIV-1 has been reported to up-regulate MHC I molecules on the surface of thymocytes from HIV-1-infected thymus. We demonstrate in this study that HIV-1 up-regulates MHC I on both HIV-1-infected and uninfected thymocytes in a manner that is independent of Nef, proportional to viral replication, and entirely mediated by IFN-alpha. IL-3Ralpha+ type 2 predendritic cells (preDC2) resident in the thymic medulla secrete IFN-alpha, which acts on IFN-alphabetaR-expressing immature thymocytes to induce MHC I expression. Furthermore, thymic preDC2 are permissive for HIV-1 infection and positive for intracellular p24. These data demonstrate the ability of IFN-alpha secreted by preDC2 to induce MHC I up-regulation in the HIV-1-infected human thymus.
Keir
Mary E
ME
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94143, USA.
Stoddart
Cheryl A
CA
Linquist-Stepps
Valerie
V
Moreno
Mary E
ME
McCune
Joseph M
JM
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D053650:Interleukin-3 Receptor alpha Subunit; D051379:Mice; D016513:Mice, SCID; D009924:Organ Culture Techniques; D012367:RNA, Viral / Q000032:analysis; D016185:Receptors, Interleukin-3 / Q000032:analysis; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000821:virology*; D015854:Up-Regulation
D016655:HIV Core Protein p24; D015395:Histocompatibility Antigens Class I; C115022:IL3RA protein, human; D016898:Interferon-alpha; D053650:Interleukin-3 Receptor alpha Subunit; D012367:RNA, Viral; D016185:Receptors, Interleukin-3