Primary Th1 cell immunization against HIVgp160 in SCID-hu mice coengrafted with peripheral blood lymphocytes and skin.
SCID-hu mouse models are of interest in the pathologic investigation of HIV infection, but obtaining a T cell response in SCID-hu-PBL mice is still controversial. We have developed a SCID model by engrafting human skin and autologous PBLs from HIV-seronegative individuals. The study describes the ability of this human-mouse chimera to generate in vivo a primary T lymphocyte response against HIV Ag. The injection of human autologous PBLs was performed 4 to 5 wk after the skin engraftment. Two weeks after injection of PBLs, chimeric mice were immunized with recombinant canary pox virus expressing HIV-1 LAIgp160 (vCP-LAIgp160) and supplemented or not with rIL-2. Intradermal vCP-LAIgp160 injection induced an intradermal perivascular human lymphocytic infiltrate and an epidermic network of CD1a+, CD80+, and CD86+ cells. We derived CD4+ T cell lines (STLs) from the human skin graft of immunized mice, showing that STLs mediated an MHC class II-restricted cytolytic activity directed against HIV-LAIgp160 Ags. Cytokine gene expression in both human skin cells and in STLs showed a predominance of IL-2, IFN-gamma, and IL-12 transcripts. Finally, the T cell repertoire analysis using the immunoscope technique showed a very limited CDR3 length polymorphism in the skin infiltrating lymphocytes suggesting an Ag-specific repertoire. The ability to induce a primary Th1 cell response in vivo affords a useful preclinical model for testing vaccine strategies.
Institut National de la Santé et de la Recherche Médicale U167, Institut Pasteur, Lille, France.
N
N
Delhem
F
F
Hadida
G
G
Gorochov
F
F
Carpentier
J P
JP
de Cavel
J F
JF
Andréani
B
B
Autran
J Y
JY
Cesbron
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D018949:Antigens, CD1 / Q000032:analysis; D000956:Antigens, Viral / Q000276:immunology; D018150:Avipoxvirus / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002678:Chimera / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007271:Injections, Intradermal; D007801:Langerhans Cells / Q000276:immunology; D007962:Leukocytes / Q000473:pathology; D017710:Lymphocyte Transfusion; D051379:Mice; D016513:Mice, SCID; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016038:Skin Transplantation / Q000276:immunology* / Q000379:methods / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*
D018949:Antigens, CD1; D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D019302:HIV Envelope Protein gp160; D011993:Recombinant Fusion Proteins