Resistance to viral infection by intraepithelial lymphocytes in HIV-1 P18-I10-specific T-cell receptor transgenic mice.
For the analysis of mucosal immunity to HIV-1, we have recently established a line of transgenic (Tg) mice expressing the TCRalpha and TCRbeta genes of the murine CTL clone RT1 specific for P18-I10 (RGPGRAFVTI), an immunodominant gp160 envelope-derived epitope of IIIB isolate, restricted by the H-2D(d) MHC-I molecule. Here we examine those cells bearing specific TCR among the intraepithelial lymphocytes (IELs), with flow cytometric analysis using H-2D(d)/P18-I10 tetramers. We observed three distinct CD3(+), tetramer positive populations among the IELs: extra-thymic CD8alphabeta(+), alphabetaTCR T-cells; CD8 alphaalpha+, gammadeltaTCR T-cells; and thymus-derived CD8alphabeta+, alphabetaTCR T-cells. Challenge of these Tg mice with P18-I10 encoded by a vaccinia virus vector, either intrarectally (i.r.) or intraperitoneally (i.p.), revealed that the intraepithelial compartment seems to be a major site for prevention of the spread of viral infection. Such immunity appears due to the thymus-derived, CD8alphabeta+ antigen-specific CTLs together with CD8alphaalpha+ gammadelta cells, which regulate virus spread. This model system for studying CTL based immunity at mucosal sites should prove helpful in developing rational approaches for HIV control.
Kuribayashi
Hideki
H
Department of Microbiology and Immunology, Nippon Medical School, Tokyo 113-8602, Japan.
Wakabayashi
Ayako
A
Shimizu
Masumi
M
Kaneko
Hiroshi
H
Norose
Yoshihiko
Y
Nakagawa
Yohko
Y
Wang
Jian
J
Kumagai
Yoshihiro
Y
Margulies
David H
DH
Takahashi
Hidemi
H
D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D005822:Genetic Vectors; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D007267:Injections; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012007:Rectum; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; C483883:P18-I10 peptide; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054301:gag Gene Products, Human Immunodeficiency Virus; C061169:p18 gag protein, Human immunodeficiency virus 1