title: Induction of MHC class I expression on immature thymocytes in HIV-1-infected SCID-hu Thy/Liv mice: evidence of indirect mechanisms.
abstract: The SCID-hu Thy/Liv mouse and human fetal thymic organ culture (HF-TOC) models have been used to explore the pathophysiologic mechanisms of HIV-1 infection in the thymus. We report here that HIV-1 infection of the SCID-hu Thy/Liv mouse leads to the induction of MHC class I (MHCI) expression on CD4+CD8+ (DP) thymocytes, which normally express low levels of MHCI. Induction of MHCI on DP thymocytes in HIV-1-infected Thy/Liv organs precedes their depletion and correlates with the pathogenic activity of the HIV-1 isolates. Both MHCI protein and mRNA are induced in thymocytes from HIV-1-infected Thy/Liv organs, indicating induction of MHCI gene expression. Indirect mechanisms are involved, because only a fraction (<10%) of the DP thymocytes were directly infected by HIV-1, although the majority of DP thymocytes are induced to express high levels of MHCI. We further demonstrate that IL-10 is induced in HIV-1-infected thymus organs. Similar HIV-1-mediated induction of MHCI expression was observed in HF-TOC assays. Exogenous IL-10 in HF-TOC induces MHCI expression on DP thymocytes. Therefore, HIV-1 infection of the thymus organ leads to induction of MHCI expression on immature thymocytes via indirect mechanisms involving IL-10. Overexpression of MHCI on DP thymocytes can interfere with thymocyte maturation and may contribute to HIV-1-induced thymocyte depletion.
authors.affiliation: Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599, USA.
authors.forename: G
authors.initials: G
authors.lastname: Kovalev
authors.forename: K
authors.initials: K
authors.lastname: Duus
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Bonyhadi
authors.forename: D
authors.initials: D
authors.lastname: Ho
authors.forename: J M
authors.initials: JM
authors.lastname: McCune
authors.forename: H
authors.initials: H
authors.lastname: Kaneshima
authors.forename: L
authors.initials: L
authors.lastname: Su
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002678:Chimera / Q000276:immunology; D005333:Fetus; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D009924:Organ Culture Techniques; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation / Q000821:virology
chemical_list: D015395:Histocompatibility Antigens Class I; D016753:Interleukin-10