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,¶
*
Institut National de la Santé et de la Recherche Médicale U167, Institut Pasteur, Lille, France;
Laboratoire d’Immunologie Cellulaire et Tissulaire, Unité de Recherche Associée 625, Centre d’Etudes et de Recherches: Virologie et Immunologie (CERVI), Hôpital Pitié-Salpétrière, Paris, France;
Service d’Anatomie et de Cytologie Pathologiques, Hôpital Victor Provo, Roubaix, France; and
§
Service de Chirurgie Maxillo Faciale, Hôpital des Armées Scrive, and
¶
Université de Lille 2, Lille, France
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-
, 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.
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