Impaired cutaneous immune responses in Thy-1-deficient mice.
Thy-1 is a cell surface glycoprotein expressed mainly on brain and lymphoid tissue. Although the functions of Thy-1 are incompletely understood, evidence exists that Thy-1 participates in T cell activation. To examine the functional role of Thy-1 in cutaneous immune responses in vivo, Thy-1 gene-targeted mice (Thy-1-/-) and wild-type mice (Thy-1+/+) were immunized with the hapten oxazolone. After challenge with oxazolone, contact hypersensitivity responses in Thy-1-/- mice were reduced by 25% compared with Thy-1+/+ mice. Likewise, irritant dermatitis induced by croton oil was also decreased. In addition, Thy-1-/- mice showed a significantly reduced delayed-type hypersensitivity response after injection of allogeneic spleen cells into the hind footpads of allosensitized animals when compared with Thy-1+/+ mice. Moreover, proliferative responses to immobilized anti-CD3 were decreased in peripheral Thy-1-/- lymphocytes; this decrease was associated with a significantly reduced intracellular Ca2+ influx and protein tyrosine phosphorylation, indicating impairment of early lymphocyte activation. In contrast, the T cell proliferation induced by mitogens was normal, suggesting that Thy-1 expression weakly contributes to TCR-mediated T cell activation. Epidermal Langerhans cells and bone marrow-derived dendritic cells from Thy-1-/- mice exhibited a normal expression of costimulatory surface molecules as well as an unaltered ability to stimulate allogeneic T cells. Taken together, these findings demonstrate that a lack of Thy-1 expression does not generally compromise the immune system; however, Thy-1 expression may be involved in the fine-tuning of T cell-mediated immune responses.
Beissert
S
S
Department of Dermatology, Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Münster, Germany.
He
H T
HT
Hueber
A O
AO
Lellouch
A C
AC
Metze
D
D
Mehling
A
A
Luger
T A
TA
Schwarz
T
T
Grabbe
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology; D003433:Crosses, Genetic; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D010766:Phosphorylation; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018800:Thy-1 Antigens / Q000235:genetics*; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D007519:Isoantigens; D018800:Thy-1 Antigens; D014443:Tyrosine; D002118:Calcium