CD8+ T-lymphocyte response to major immunodominant epitopes after vaginal exposure to simian immunodeficiency virus

Too late and too little

Matthew R. Reynolds, Eva Rakasz, Pamela J. Skinner, Cara White, Kristina Abel, Zhong Min Ma, Lara Compton, Gnankang Napoé, Nancy Wilson, Chris J Miller, Ashley Haase, David I. Watkins

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

In the acute stage of infection following sexual transmission of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), virus-specific CD8+ T-lymphocyte responses partially control but do not eradicate infection from the lymphatic tissues (LTs) or prevent the particularly massive depletion of CD4+ T lymphocytes in gut-associated lymphatic tissue (GALT). We explored hypothetical explanations for this failure to clear infection and prevent CD4+ T-lymphocyte loss in the SIV/rhesus macaque model of intravaginal transmission. We examined the relationship between the timing and magnitude of the CD8+ T-lymphocyte response to immunodominant SFV epitopes and viral replication, and we show first that the failure to contain infection is not because the female reproductive tract is a poor inductive site. We documented robust responses in cervicovaginal tissues and uterus, but only several days after the peak of virus production. Second, while we also documented a modest response in the draining genital and peripheral lymph nodes, the response at these sites also lagged behind peak virus production in these LT compartments. Third, we found that the response in GALT was surprisingly low or undetectable, possibly contributing to the severe and sustained depletion of CD4+ T lymphocytes in the GALT. Thus, the virus-specific CD8+ T-lymphocyte response is "too late and too little" to clear infection and prevent CD4+ T-lymphocyte loss. However, the robust response in female reproductive tissues may be an encouraging sign that vaccines that rapidly induce high-frequency CD8+ T-lymphocyte responses might be able to prevent acquisition of HIV-1 infection by the most common route of transmission.

Original languageEnglish (US)
Pages (from-to)9228-9235
Number of pages8
JournalJournal of Virology
Volume79
Issue number14
DOIs
StatePublished - Jul 2005

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Simian immunodeficiency virus
Immunodominant Epitopes
Simian Immunodeficiency Virus
T-lymphocytes
Lymphoid Tissue
T-Lymphocytes
infection
Viruses
Infection
viruses
digestive system
immunodominant epitopes
Human immunodeficiency virus
Virus Diseases
virus replication
Human immunodeficiency virus 1
Macaca mulatta
tissues
uterus
genitalia

ASJC Scopus subject areas

  • Immunology

Cite this

CD8+ T-lymphocyte response to major immunodominant epitopes after vaginal exposure to simian immunodeficiency virus : Too late and too little. / Reynolds, Matthew R.; Rakasz, Eva; Skinner, Pamela J.; White, Cara; Abel, Kristina; Ma, Zhong Min; Compton, Lara; Napoé, Gnankang; Wilson, Nancy; Miller, Chris J; Haase, Ashley; Watkins, David I.

In: Journal of Virology, Vol. 79, No. 14, 07.2005, p. 9228-9235.

Research output: Contribution to journalArticle

Reynolds, MR, Rakasz, E, Skinner, PJ, White, C, Abel, K, Ma, ZM, Compton, L, Napoé, G, Wilson, N, Miller, CJ, Haase, A & Watkins, DI 2005, 'CD8+ T-lymphocyte response to major immunodominant epitopes after vaginal exposure to simian immunodeficiency virus: Too late and too little', Journal of Virology, vol. 79, no. 14, pp. 9228-9235. https://doi.org/10.1128/JVI.79.14.9228-9235.2005
Reynolds, Matthew R. ; Rakasz, Eva ; Skinner, Pamela J. ; White, Cara ; Abel, Kristina ; Ma, Zhong Min ; Compton, Lara ; Napoé, Gnankang ; Wilson, Nancy ; Miller, Chris J ; Haase, Ashley ; Watkins, David I. / CD8+ T-lymphocyte response to major immunodominant epitopes after vaginal exposure to simian immunodeficiency virus : Too late and too little. In: Journal of Virology. 2005 ; Vol. 79, No. 14. pp. 9228-9235.
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AU - Ma, Zhong Min

AU - Compton, Lara

AU - Napoé, Gnankang

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AU - Miller, Chris J

AU - Haase, Ashley

AU - Watkins, David I.

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