Vaccine-Induced CD107a + CD4 + T Cells Are Resistant to Depletion following AIDS Virus Infection

Author:

Terahara Kazutaka1,Ishii Hiroshi2,Nomura Takushi2,Takahashi Naofumi2,Takeda Akiko2,Shiino Teiichiro2,Tsunetsugu-Yokota Yasuko1,Matano Tetsuro23

Affiliation:

1. Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan

2. AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan

3. The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Abstract

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. IMPORTANCE 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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