Newcastle disease virus infection induces B7-1/B7-2-independent T-cell costimulatory activity in human melanoma cells.
Viral oncolysates of Newcastle disease virus (NDV) have been widely used for the treatment of malignant melanoma. Apparently, this nononcogenic and apathogenic paramyxovirus can alter the immunogenicity of tumor cells. To determine the influence of NDV infection on a tumor-specific T-cell response on a functional level, we used autologous primary melanoma cells infected with the NDV-strain Ulster. Therefore, melanoma cells and tumor-infiltrating lymphocytes were prepared from a freshly resected tumor, and tumor-infiltrating lymphocytes were subjected to limited dilution cloning. Proliferation assays of the T-helper cell clone sTS3 (CD4+) showed that the T-cell clone was rendered nonreactive against its autologous major histocompatibility complex II+, B7-1/B7-2- melanoma SMS, even remaining unresponsive to subsequent stimulation by interleukin-2. NDV infection of the SMS melanoma cell line not only completely restored the proliferative response of sTS3 to SMS, comparable with stimulation by cross-linking of anti-CD3/anti-CD28 monoclonal antibodies, but also inhibited the induction of anergy. Electrophoretic mobility shift assays of sTS3 cell lysates revealed the induction of the CD28-responsive complex by coincubation with NDV-infected melanoma cells. Because the induction of this complex of nuclear proteins shows specificity for the activation of the CD28 pathway but functional B7-1/B7-2 expression was not detectable on SMS melanoma cells at any timepoint, we propose the induction of a costimulatory factor different from B7 by NDV viral proteins.
Termeer
C C
CC
Department of Dermatology, University of Freiburg, Germany.
Schirrmacher
V
V
Bröcker
E B
EB
Becker
J C
JC
D015703:Antigens, CD / Q000502:physiology*; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics; D002999:Clone Cells; D005786:Gene Expression Regulation; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000821:virology; D008545:Melanoma / Q000276:immunology* / Q000821:virology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D009522:Newcastle disease virus / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000821:virology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins