TY - JOUR
T1 - Characterization of a T cell line bearing natural killer receptors and capable of creating psoriasis in a SCID mouse model system
AU - Nickoloff, Brian J.
AU - Bonish, Brian
AU - Huang, Barbara Bei
AU - Porcelli, Steven A.
N1 - Funding Information:
The authors thank Patricia Bacon for performing immunohistochemical staining, Jeff Panella for performing the RPAs, and Heide Bauer and Crystal Tabor for manuscript and figure preparation. Drs Kevin Cooper and Zsuzsanna Bata-Csorgo (Case Western Reserve University) kindly provided the IFN-γ producing CD4+ T cell clones 4F4 and 4F1. This work was supported by NIH Grant AR40065 (B.J. Nickoloff).
PY - 2000
Y1 - 2000
N2 - 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-γ 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-γ 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-γ. 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. (C) 2000 Elsevier Science Ireland Ltd.
AB - 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-γ 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-γ 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-γ. 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. (C) 2000 Elsevier Science Ireland Ltd.
KW - Natural killer receptors
KW - Psoriasis
KW - SCID mouse model system
KW - T cell
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U2 - 10.1016/S0923-1811(00)00120-1
DO - 10.1016/S0923-1811(00)00120-1
M3 - Article
C2 - 11084303
AN - SCOPUS:0033748019
SN - 0923-1811
VL - 24
SP - 212
EP - 225
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
IS - 3
ER -