Functional reconstitution of class II MHC-restricted T cell immunity mediated by retroviral transfer of the alpha beta TCR complex.
Transfer of the alphabeta TCR genes into T lymphocytes will provide a means to enhance Ag-specific immunity by increasing the frequency of tumor- or pathogen-specific T lymphocytes. We generated an efficient alphabeta TCR gene transfer system using two independent monocistronic retrovirus vectors harboring either of the class II MHC-restricted alpha or beta TCR genes specific for chicken OVA. The system enabled us to express the clonotypic TCR in 44% of the CD4+ T cells. The transduced cells showed a remarkable response to OVA323-339 peptide in the in vitro culture system, and the response to the Ag was comparable with those of the T lymphocytes derived from transgenic mice harboring OVA-specific TCR. Adoptive transfer of the TCR-transduced cells in mice induced the Ag-specific delayed-type hypersensitivity in response to OVA323-339 challenge. These results indicate that alphabeta TCR gene transfer into peripheral T lymphocytes can reconstitute Ag-specific immunity. We here propose that this method provides a basis for a new approach to manipulation of immune reactions and immunotherapy.
Fujio
K
K
Department of Hematopoietic Factors, Institute of Medical Science, University of Tokyo, Japan.
Misaki
Y
Y
Setoguchi
K
K
Morita
S
S
Kawahata
K
K
Kato
I
I
Nosaka
T
T
Yamamoto
K
K
Kitamura
T
T
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D002999:Clone Cells; D005260:Female; D018014:Gene Transfer Techniques; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D005822:Genetic Vectors / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas / Q000378:metabolism; D007111:Immunity, Cellular / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; C111390:OVA 323-339; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin