Blockade of CD2-LFA-3 interactions protects human skin allografts in immunodeficient mouse/human chimeras.
A human skin allograft injury model in immunodeficient mice, engrafted with human peripheral blood mononuclear cells from a different donor, has been used to test whether reagents that block human T cell CD2 interactions with its principal ligand, LFA-3 (CD58), can inhibit immune reactions in vivo. In this model, human skin grafts show a reproducible pattern of progressive human T-cell infiltration and human graft microvascular injury that resembles human first-set skin graft rejection. Murine Mab to human LFA-3 or human LFA-3-IgG1 fusion protein, but not isotype-matched control antibodies, each markedly protected skin grafts from leukocyte infiltration and injury. These data provide the first evidence that LFA-3 functions in vivo and establish the ability of this new model to test human-specific immune modulators.
Sultan
P
P
Molecular Cardiobiology Program, Yale University School of Medicine, New Haven, CT 06536, USA.
Schechner
J S
JS
McNiff
J M
JM
Hochman
P S
PS
Hughes
C C
CC
Lorber
M I
MI
Askenase
P W
PW
Pober
J S
JS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D018801:CD2 Antigens / Q000378:metabolism*; D018968:CD58 Antigens / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D018968:CD58 Antigens; D007074:Immunoglobulin G