Protection from lethal infection by adoptive transfer of CD8 T cells genetically engineered to express virus-specific innate immune receptor
| Autor: | Koho Iizuka, Yoshie-Matsubayashi Iizuka, Osami Kanagawa, Mitsuyo Takase, Kazuo Tanaka, Chigusa Nakajima, Takako Kato, Satoshi Noda |
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| Předmět: |
Muromegalovirus
Adoptive cell transfer CD3 Complex Immunology Receptors Antigen T-Cell CD8-Positive T-Lymphocytes Biology Protein Engineering Polymerase Chain Reaction Virus Mice Immune system Animals Antigens Ly Immunology and Allergy Cytotoxic T cell Lectins C-Type Receptors Immunologic Receptor Mice Inbred BALB C Innate immune system Chimera virus diseases Herpesviridae Infections Adoptive Transfer Virology Killer Cells Natural Viral replication NK Cell Lectin-Like Receptor Subfamily A CD8 Receptors NK Cell Lectin-Like |
| Zdroj: | Scopus-Elsevier |
| Popis: | CMV infection is one of the most common complications in immunocompromised individuals, such as organ and bone marrow transplant patients. Both innate and adaptive immune responses are required for defense against CMV infection. In murine CMV (MCMV) infection, strains harboring the MCMV-specific NK cell activation receptor, Ly49H (Klra8), are resistant. In contrast, MCMV infection of mice lacking Ly49H gene causes early mortality due to uncontrolled viral replication. In this study, we report the successful protection of mice from lethal MCMV infection with gene-transferred polyclonal CD8 T cells. CD8 T cells expressing a chimeric receptor comprising Ly49H extracellular and CD3ζ cytoplasmic domains are capable of killing target cells expressing the MCMV protein, m157. CD8 T cells expressing the chimeric receptor protect mice in vivo from lethality in the acute phase of MCMV infection, leading to the establishment of long-term protection. These data provide proof-of-principle evidence that a novel strategy for harnessing CD8 cytolytic function through TCR-independent yet pathogen-specific receptor can result in effective protection of hosts from pathogens. |
| Databáze: | OpenAIRE |
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