Chimeric immune receptor T cells bypass class I requirements and recognize multiple cell types relevant in HIV-1 infection.
Transduction of T cells with a chimeric immune T cell receptor (CIR) has been proposed as a strategy to generate cellular immunity against viral pathogens such as HIV-1. In the case of the CD4-CD3-zeta chain (CD4-zeta) CIR, specificity for HIV-1 is conferred by binding of the CD4 moiety to gp120 on the surface of infected cells. However, it is unclear whether CD4-zeta-T cells may differ from naturally derived CD8(+) cytotoxic T cells (CTL) in their susceptibility to viral escape mechanisms or ability to recognize different cell types that support viral replication. We demonstrate that CIR-T cells can mediate antiviral activity against HIV-1 in cells that are resistant to class I-restricted CTL-mediated activity. Furthermore, CIR-T cells can suppress virus in multiple cell types, including monocytes, dendritic cells, and lymphocyte-dendritic cell clusters. These results provide evidence that T cells can be redirected against novel targets, and that independence from the class I pathway may have distinct advantages.
Severino
Michael E
ME
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Sarkis
Phuong Thi Nguyen
PT
Walker
Bruce D
BD
Yang
Otto O
OO
D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D015316:Genetic Therapy; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D009000:Monocytes / Q000276:immunology / Q000821:virology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic; D014779:Virus Replication
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins