Characterization of a T cell line bearing natural killer receptors and capable of creating psoriasis in a SCID mouse model system.
T cells bearing natural killer receptors (NKRs) such as CD94 and CD161 are present in psoriasis. These immunocytes express several receptors for both classical and non-classical class I MHC molecules. Whether T cells bearing NKRs in psoriatic lesions represent immunoregulatory versus pathogenic immunocytes or are just bystander cells is unclear. To address this issue, a CD94+/CD161+ T cell line was established from a psoriatic patient using IL-2/superantigens, and the interaction between NK-T cells and keratinocytes was characterized using in-vitro and in-vivo assays. Upon incubation between NK-T cells and CD1d positive keratinocytes, high levels of IFN-gamma and IL-13 were produced. Cytokine production was inhibited by a mAb against CD1d, implicating recognition of this surface molecule in the T cell response. Furthermore when this line was injected into pre-psoriatic skin engrafted onto a SCID mouse, a psoriatic plaque was created. The hyperplastic epidermal keratinocytes diffusely expressed CD1d, and were infiltrated by CD161+ T cells. RNase protection assay revealed predominantly IFN-gamma and IL-15 mRNAs, with barely detectable IL-13 mRNA in the acute lesion. These in-vivo findings demonstrated that this T cell line was pathogenic by creating a psoriatic plaque. The in-vitro results support a pathophysiologic role for interaction between T cells expressing NKRs and CD1d positive keratinocytes, with subsequent production of IFN-gamma. Upon injection in-vivo, the cytokine network produced was characterized by an immunological response polarized towards Th1 rather than Th2 cytokines. Thus, this pathogenic cell line provides evidence that T cells bearing NKRs can directly provoke a Th1 disease such as psoriasis.
Nickoloff
B J
BJ
Department of Pathology, Loyola University Medical Center, Boston, MA 60153-5385, USA. bnickol@lumc.edu
Bonish
B
B
Huang
B B
BB
Porcelli
S A
SA
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D055651:NK Cell Lectin-Like Receptor Subfamily B; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011565:Psoriasis / Q000209:etiology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D015703:Antigens, CD; D000954:Antigens, Surface; C527203:KLRB1 protein, human; C497869:KLRD1 protein, human; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D051920:NK Cell Lectin-Like Receptor Subfamily D