Reconstitution of anti-HIV effector functions of primary human CD8 T lymphocytes by transfer of HIV-specific alphabeta TCR genes.
We redirected the antigen specificity of primary human CD8 T cells by retrovirus-mediated transduction of genes encoding alphabeta TCR specific to HIV-1 Pol protein. A large polyclonal population of TCR-transduced CD8 T cells showed substantial cytotoxic and cytokine production activities toward target cells either pulsed with the peptide or infected with HIV-1, and their functional activities were comparable to those of the parental CTL clone. Peptide fine-specificity and promiscuous recognition of HLA class I supertypes of the parental CTL clone were also preserved in the TCR-transduced cells. There were no signs of allogeneic responses in these cells, although hybrid TCR dimers consisting of transduced TCR and endogenous TCR were suspected to have been formed in these cells, as the effect of transgene expression on the surface expression of the desired TCR was limited. Moreover, the TCR-transduced cells showed potent inhibitory activity against HIV-1 replication in vitro, although the differential surface expression of the desired TCR resulted in differential functional avidity of individual TCR-transduced cells toward the peptide-pulsed target cells. These data suggest that the reconstitution of HIV-specific immunoreactive T cells engineered by genetic transfer of HIV-specific TCR is a potential alternative to immunotherapeutic applications against HIV infections.
Ueno
Takamasa
T
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan. uenot@kaiju.medic.kumamoto-u.ac.jp
Fujiwara
Mamoru
M
Tomiyama
Hiroko
H
Onodera
Masafumi
M
Takiguchi
Masafumi
M
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D015684:Gene Products, pol / Q000276:immunology; D015316:Genetic Therapy; D005822:Genetic Vectors; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012190:Retroviridae; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic
D015684:Gene Products, pol; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta