Non-replicating recombinant vaccinia virus encoding murine B-7 molecules elicits effective costimulation of naive CD4+ splenocytes in vitro.
Using a series of new insertion/expression vectors, we constructed a set of recombinant vaccinia viruses (recVV) encoding the murine T cell costimulatory molecules mB7-1 or mB7-2, or both together in the same construct. On infection with replication incompetent and non-cytopathic recVV, several tumour cell lines expressed the respective molecules and bound to CTLA-4. The highest binding capacity was found when both mB7 molecules were co-expressed. Mouse B16.F10 melanoma cells expressing mB7-1 or mB7-2 provided effective costimulation for proliferation of resting CD4+ T cells in the presence of concanavalin A and plate-bound anti-T cell receptor antibodies, respectively. If mB7-1 and mB7-2 were delivered together on the same cell, the proliferative response of CD4+ T cells increased further. The costimulatory effect could be blocked with CTLA-4, the soluble ligand for B7 molecules. The possibility of engineering tumour cells using recVV holds implications for the future design of vaccination strategies.
Oertli
D
D
Department of Surgery, University Hospital of Basel, Switzerland.
Marti
W R
WR
Norton
J A
JA
Tsung
K
K
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D051940:B7-2 Antigen; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D004247:DNA; D005822:Genetic Vectors; D006801:Humans; D018796:Immunoconjugates; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics* / Q000502:physiology; D014779:Virus Replication
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D000069594:Abatacept; D004247:DNA