Porcine thymic grafts protect human thymocytes from HIV-1-induced destruction.
Human immunodeficiency virus type 1 (HIV-1) infection depletes thymocytes and destroys thymic structure. Functional, tolerant human T cells develop in vivo in immunodeficient mice receiving porcine thymus and human fetal liver fragments under the kidney capsule. In this model, we evaluated the potential of porcine thymus to protect human thymocytes from the effects of HIV-1. Compared with that observed in control mice with human thymic grafts, porcine thymus attenuated human thymocyte depletion by the CCR5-tropic isolate JR-CSF without preventing thymocyte infection. Porcine thymus protected human thymocytes from infection and depletion by a CXCR4-tropic HIV-1 isolate without reducing peripheral blood viral loads or T cell infection. Human thymocytes from human but not porcine grafts showed decreased Bcl-2 expression and increased apoptosis after NL4.3 infection. Thus, porcine thymus protects human thymocytes from the cytopathic effect of HIV-1, suggesting a possible approach to achieving immune restoration in patients with acquired immunodeficiency syndrome who have incomplete responses to antiretroviral therapy. The model allows analysis of the mechanisms of HIV-mediated thymic dysfunction.
Hongo
David
D
Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
Hadidi
Sima
S
Damrauer
Scott
S
Garrigue
Valerie
V
Kraft
Daniel
D
Sachs
David H
DH
Nikolic
Boris
B
Sykes
Megan
M
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D003588:Cytopathogenic Effect, Viral; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D016332:Fetal Tissue Transplantation; D005333:Fetus / Q000166:cytology; D015870:Gene Expression; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D014183:Transplantation, Heterologous; D019562:Viral Load
D018952:Antigens, CD34; D019253:Proto-Oncogene Proteins c-bcl-2