Vaccine-induced CD107a+ CD4+ T cells are resistant to depletion following AIDS virus infection

• Published in: Journal of virology Vol. 88; no. 24; pp. 14232 - 14240
• Main Authors: Terahara, Kazutaka, Ishii, Hiroshi, Nomura, Takushi, Takahashi, Naofumi, Takeda, Akiko, Shiino, Teiichiro, Tsunetsugu-Yokota, Yasuko, Matano, Tetsuro
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.12.2014
• Subjects: AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; Animals; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - chemistry; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; HIV - growth & development; Human immunodeficiency virus; Lymphocyte Subsets - chemistry; Lymphocyte Subsets - immunology; Lymphocyte Subsets - virology; Lysosomal-Associated Membrane Protein 1 - analysis; Macaca; Macaca mulatta; Vaccines and Antiviral Agents
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.02032-14

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. 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.