Immunological characterization of human vaginal xenografts in immunocompromised mice: development of a small animal model for the study of human immunodeficiency virus-1 infection.
A small animal model for the in vivo study of human immunodeficiency virus-1 and other fastidious infectious agents in human host target tissues is critical for the advancement of therapeutic and preventative strategies. Our laboratory has developed a human vaginal xenograft model that histologically recapitulates features of the human vaginal epithelial barrier. Vaginal xenografts were surgically implanted into C.B.-Igh-1(b)/IcrTac-Prkdc(scid) (SCID) and NOD/LtSz-scid/scid (NOD/SCID) mice, with and without human peripheral blood mononuclear cell reconstitution. Immunohistochemical staining of vaginal xenografts demonstrated that in the SCID strain healed vaginal xenografts did not retain intrinsic human immune cells at baseline levels, whereas the NOD/SCID strain supported retention of intrinsic human immune cell populations within the xenografts for at least 2 months after engraftment. In peripheral blood mononuclear cell-reconstituted NOD/SCID mice with vaginal xenografts, flow cytometric analyses detected human immune cell populations in the peripheral blood and immunohistochemical methods detected infiltration of human CD45+ cells in the mouse spleens and vaginal xenografts for at least 2 months after reconstitution. This optimized NOD/SCID human vaginal xenograft model may provide a unique small animal in vivo system for the study of human immunodeficiency virus-1 transmission and infection.
Kish
T M
TM
Department of Microbiology and Immunology, the Milton S. Hershey Medical Center, The Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Budgeon
L R
LR
Welsh
P A
PA
Howett
M K
MK
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016867:Immunocompromised Host; D017493:Leukocyte Common Antigens / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D017464:Receptors, Complement 3d / Q000032:analysis; D013045:Species Specificity; D013997:Time Factors; D016378:Tissue Transplantation; D014183:Transplantation, Heterologous; D014621:Vagina / Q000276:immunology* / Q000601:surgery; D014945:Wound Healing; D000097382:CD68 Molecule
D015703:Antigens, CD; D018949:Antigens, CD1; D015214:Antigens, Differentiation, Myelomonocytic; D015704:CD4 Antigens; D016827:CD8 Antigens; D017493:Leukocyte Common Antigens; D017464:Receptors, Complement 3d; C419393:CD1a antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule