title: Normal development and function but impaired memory phenotype of CD8⁺ T cells in transgenic mice expressing HIV-1 Nef in its natural target cells.
abstract: We studied the impact of HIV Nef on CD8(+) T cells in a mouse model of AIDS, the CD4C/HIV(Nef) transgenic (Tg) mice. We found that negative and positive thymic selections of CD8(+) T cells proceeded normally in Nef Tg mice bred respectively with HY or OT-1 TCR Tg mice. Tg peripheral CD8(+) T cells showed an activated phenotype and enhanced cell division in vivo and proliferated efficiently when stimulated in vitro with antigenic peptide. When challenged with LCMV(Armstrong), Nef Tg mice developed a strong acute CD8(+) T cell response and cleared the virus as efficiently as wild-type mice. However, maintenance of LCMV-specific CD8(+) memory T cells was impaired in Nef Tg mice, a defect partially rescued by adoptive transfer of non-Tg naïve CD4(+) T cells. Thus, despite severe abnormalities of their precursors, the double-positive CD4(+)CD8(+) thymocytes, Tg CD8(+) T cells have conserved important functions.
authors: Laboratory of Molecular Biology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada.
authors: Mir Munir
authors: MM
authors: Ahmed Rahim
authors: Pavel
authors: P
authors: Chrobak
authors: Elena
authors: E
authors: Priceputu
authors: Zaher
authors: Z
authors: Hanna
authors: Paul
authors: P
authors: Jolicoeur
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1