title: Vaccine-induced CD107a+ CD4+ T cells are resistant to depletion following AIDS virus infection.
abstract: CD4(+) T-cell responses are crucial for effective antibody and CD8(+) T-cell induction following virus infection. However, virus-specific CD4(+) T cells can be preferential targets for human immunodeficiency virus (HIV) infection. HIV-specific CD4(+) T-cell induction by vaccination may thus result in enhancement of virus replication following infection. In the present study, we show that vaccine-elicited CD4(+) T cells expressing CD107a are relatively resistant to depletion in a macaque AIDS model. Comparison of virus-specific CD107a, macrophage inflammatory protein-1β, gamma interferon, tumor necrosis factor alpha, and interleukin-2 responses in CD4(+) T cells of vaccinated macaques prechallenge and 1 week postchallenge showed a significant reduction in the CD107a(-) but not the CD107a(+) subset after virus exposure. Those vaccinees that failed to control viremia showed a more marked reduction and exhibited significantly higher viral loads at week 1 than unvaccinated animals. Our results indicate that vaccine-induced CD107a(-) CD4(+) T cells are depleted following virus infection, suggesting a rationale for avoiding virus-specific CD107a(-) CD4(+) T-cell induction in HIV vaccine design.
  
  
  OBJECTIVE
  Induction of effective antibody and/or CD8(+) T-cell responses is a principal vaccine strategy against human immunodeficiency virus (HIV) infection. CD4(+) T-cell responses are crucial for effective antibody and CD8(+) T-cell induction. However, virus-specific CD4(+) T cells can be preferential targets for HIV infection. Here, we show that vaccine-induced virus-specific CD107a(-) CD4(+) T cells are largely depleted following infection in a macaque AIDS model. While CD4(+) T-cell responses are important in viral control, our results indicate that virus-specific CD107a(-) CD4(+) T-cell induction by vaccination may not lead to efficient CD4(+) T-cell responses following infection but rather be detrimental and accelerate viral replication in the acute phase. This suggests that HIV vaccine design should avoid virus-specific CD107a(-) CD4(+) T-cell induction. Conversely, this study found that vaccine-induced CD107a(+) CD4(+) T cells are relatively resistant to depletion following virus challenge, implying that induction of these cells may be an alternative approach toward HIV control.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Terahara
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Takushi
authors.initials: T
authors.lastname: Nomura
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeda
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Teiichiro
authors.initials: T
authors.lastname: Shiino
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tsunetsugu-Yokota
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan The Institute of Medical Science, The University of Tokyo, Tokyo, Japan tmatano@nih.go.jp.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000821:virology*; D006678:HIV / Q000254:growth & development*; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology* / Q000821:virology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000032:analysis*; D008253:Macaca mulatta
chemical_list: D016915:AIDS Vaccines; D052118:Lysosomal-Associated Membrane Protein 1