title: Apoptosis of antigen-specific CTLs contributes to low immune response in gut-associated lymphoid tissue post vaccination.
abstract: The gut-associated lymphoid tissue (GALT) represents a major reservoir of HIV in infected individuals. Vaccines can induce strong systemic immune responses but these have less impact on CD4 T cells activity and numbers in GALT. In this study, we vaccinated mice with an adenovirus vector that expressed the envelope gene from HIV and observed immune responses in the peripheral blood, spleen, liver, mesenteric lymph nodes, and Peyer's patches. We found that (1) the number of HIV-specific CD8 T cells was dramatically lower in GALT than in other tissues; (2) the programmed cell death protein-1 (PD-1) was expressed at high levels in HIV-specific CD8 T cells including memory T cells in GALT; and (3) high levels of HIV-specific CD8 T cell apoptosis were occurring in GALT. These results suggest that contributing to GALT becoming an HIV reservoir during infection is a combination of exhaustion and/or dysfunction of HIV-specific CTLs at that site. These results emphasize the importance of developing of an effective mucosal vaccine against HIV.
authors: Department of Molecular Biodefense Research, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: mshimada@yokohama-cu.ac.jp.
authors: Masaru
authors: M
authors: Shimada
authors: Department of Molecular Biodefense Research, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Shinji
authors: S
authors: Yoshizaki
authors: Department of Immunology, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Motohide
authors: M
authors: Ichino
authors: Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, United States.
authors: Dennis M
authors: DM
authors: Klinman
authors: Department of Molecular Biodefense Research, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Kenji
authors: K
authors: Okuda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D061026:Programmed Cell Death 1 Receptor
keywords: Mouse; Programmed cell death protein-1 (PD-1); Vaccine; Virus vector