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 o f HIV infection, but obtaining a T cell response in SCID-hu-PBL mice i s still controversial. We have developed a SCID model by engrafting hu man skin and autologous PBLs from HIV-seronegative individuals. The st udy describes the ability of this human-mouse chimera to generate in v ivo a primary T lymphocyte response against HIV Ag. The injection of h uman autologous PBLs was performed 4 to 5 wk after the skin engraftmen t. Two weeks after injection of PBLs, chimeric mice were immunized wit h recombinant canary pox virus expressing HIV-1 LAIgp160 (vCP-LAIgp160 ) and supplemented or not with rIL-2, Intradermal vCP-LAIgp160 injecti on induced an intradermal perivascular human lymphocytic infiltrate an d an epidermic network of CD1a(+), CD80(+), and CD86(+) cells. We deri ved 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 i n 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 pol ymorphism in the skin infiltrating lymphocytes suggesting an Ag-specif ic repertoire. The ability to induce a primary Th1 cell response in vi vo affords a useful preclinical model for testing vaccine strategies.