Summary of the publications
Nozomi Kuse, Hiroyuki Gatanaga, Yu Zhang, Takayuki Chikata, Shinichi Oka, and Masafumi Takiguchi, Epitope-dependent effect of long-term cART on maintenance and recovery of HIV-1-specific CD8+ T cells. J. Virol. 97: e0102423, 2023
HIV-1-specific CD8+ T cells are anticipated to become effector cells for curative treatment using the "shock and kill" approach in people living with HIV-1 (PLWH) under combined antiretroviral therapy (cART). Previous studies demonstrated that the frequency of HIV-1-specific CD8+ T cells is reduced under cART and their functional ability remains impaired. These studies analyzed T-cell responses to a small number of HIV-1 epitopes or overlapping HIV-1 peptides. Therefore, the features of CD8+ T cells specific for HIV-1 epitopes under cART remain only partially clarified. Here, we analyzed CD8+ T cells specific for 63 well-characterized epitopes in 90 PLWH. We demonstrated that CD8+ T cells specific for large numbers of HIV-1 epitopes were maintained in an epitope-dependent fashion under long-term cART and that long-term cART enhanced or restored the ability of HIV-1-specific T cells to proliferate in vitro. This study implies that some HIV-1-specific T cells would be useful as effector cells for curative treatment.
Takayuki Chikata, Hiroyuki Gatanaga, Hung The Nguyen, Daisuke Mizushima, Yu Zhang, Nozomi Kuse, Shinichi Oka, and Masafumi Takiguchi, HIV-1 protective epitope-specific CD8+ T cells in HIV-1-exposed seronegative individuals. iScience 26: 108089, 2023
Although previous studies have reported HIV-1-specific T cell responses in HIV-1-exposed seronegative (HESN) individuals, there has been no detailed analysis of these T cells against HIV-1 infection. We investigated HIV-1-specific CD8+ T cell responses in 200 Japanese HESN men who have sex with men (MSM). T cell responses to 143 well-characterized HIV-1 epitope peptides were analyzed by intracellular cytokine staining assay consisting of 3-week cultures of PBMCs stimulated with peptides. HLA-B*51:01-restricted Pol TI8-specific and HLA-A?02:06-restricted Pol SV9-specific CD8+ T cells were identified in two and one individuals, respectively, whereas CD8+ T cells specific for other HLA-A*02:06-restricted or HLA-B*51:01 epitopes were not present in these individuals. These epitope-specific T cells recognized HIV-1-infected cells. Because these two epitopes were previously reported to be protective in HIV-1-infected individuals, these protective epitope-specific T cells might suppress HIV-1 replication in HESN-MSM individuals. The present study suggests the contribution of protective epitope-specific T cells to protection against HIV-1 infection.