Impairment of Gag-specific CD8+ T-cell function in mucosal and systemic compartments of simian immunodeficiency virus mac251- and simian-human immunodeficiency virus KU2-infected macaques

Z. Hel, J. Nacsa, B. Kelsall, W. P. Tsai, N. Letvin, R. W. Parks, E. Tryniszewska, L. Picker, M. G. Lewis, Y. Edghill-Smith, M. Moniuszko, R. Pal, L. Stevceva, J. D. Altman, T. M. Allen, D. Watkins, Jose V Torres, J. A. Berzofsky, I. M. Belyakov, W. Strober & 1 others G. Franchini

Research output: Contribution to journalArticle

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Abstract

The identification of several simian immunodeficiency virus mac251 (SIVmac251) cytotoxic T-lymphocyte epitopes recognized by CD8+ T cells of infected rhesus macaques carrying the Mamu-A*01 molecule and the use of peptide-major histocompatibility complex tetrameric complexes enable the study of the frequency, breadth, functionality, and distribution of virus-specific CD8+ T cells in the body. To begin to address these issues, we have performed a pilot study to measure the virus-specific CD8+ and CD4+ T-cell response in the blood, lymph nodes, spleen, and gastrointestinal lymphoid tissues of eight Mamu-A*01-positive macaques, six of those infected with SIVmac251 and two infected with the pathogenic simian-human immunodeficiency virus KU2. We focused on the analysis of the response to peptide p11C, C-M (Gag 181), since it was predominant in most tissues of all macaques. Five macaques restricted viral replication effectively, whereas the remaining three failed to control viremia and experienced a progressive loss of CD4+ T cells. The frequency of the Gag 181 (p11C, C→M) immunodominant response varied among different tissues of the same animal and in the same tissues from different animals. We found that the functionality of this virus-specific CD8+ T-cell population could not be assumed based on the ability to specifically bind to the Gag 181 tetramer, particularly in the mucosal tissues of some of the macaques infected by SIVmac251 that were progressing to disease. Overall, the functionality of CD8+ tetramer-binding T cells in tissues assessed by either measurement of cytolytic activity or the ability of these cells to produce gamma interferon or tumor necrosis factor alpha was low and was even lower in the mucosal tissue than in blood or spleen of some SIVmac251-infected animals that failed to control viremia. The data obtained in this pilot study lead to the hypothesis that disease progression may be associated with loss of virus-specific CD8+ T-cell function.

Original languageEnglish (US)
Pages (from-to)11483-11495
Number of pages13
JournalJournal of Virology
Volume75
Issue number23
DOIs
StatePublished - 2001
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Human immunodeficiency virus
Macaca
T-lymphocytes
HIV
T-Lymphocytes
Viruses
viruses
Viremia
viremia
spleen
Mucous Membrane
Spleen
peptides
cytotoxic T-lymphocytes
T-Lymphocyte Epitopes
animal tissues
blood
major histocompatibility complex

ASJC Scopus subject areas

  • Immunology

Cite this

Impairment of Gag-specific CD8+ T-cell function in mucosal and systemic compartments of simian immunodeficiency virus mac251- and simian-human immunodeficiency virus KU2-infected macaques. / Hel, Z.; Nacsa, J.; Kelsall, B.; Tsai, W. P.; Letvin, N.; Parks, R. W.; Tryniszewska, E.; Picker, L.; Lewis, M. G.; Edghill-Smith, Y.; Moniuszko, M.; Pal, R.; Stevceva, L.; Altman, J. D.; Allen, T. M.; Watkins, D.; Torres, Jose V; Berzofsky, J. A.; Belyakov, I. M.; Strober, W.; Franchini, G.

In: Journal of Virology, Vol. 75, No. 23, 2001, p. 11483-11495.

Research output: Contribution to journalArticle

Hel, Z, Nacsa, J, Kelsall, B, Tsai, WP, Letvin, N, Parks, RW, Tryniszewska, E, Picker, L, Lewis, MG, Edghill-Smith, Y, Moniuszko, M, Pal, R, Stevceva, L, Altman, JD, Allen, TM, Watkins, D, Torres, JV, Berzofsky, JA, Belyakov, IM, Strober, W & Franchini, G 2001, 'Impairment of Gag-specific CD8+ T-cell function in mucosal and systemic compartments of simian immunodeficiency virus mac251- and simian-human immunodeficiency virus KU2-infected macaques', Journal of Virology, vol. 75, no. 23, pp. 11483-11495. https://doi.org/10.1128/JVI.75.23.11483-11495.2001
Hel, Z. ; Nacsa, J. ; Kelsall, B. ; Tsai, W. P. ; Letvin, N. ; Parks, R. W. ; Tryniszewska, E. ; Picker, L. ; Lewis, M. G. ; Edghill-Smith, Y. ; Moniuszko, M. ; Pal, R. ; Stevceva, L. ; Altman, J. D. ; Allen, T. M. ; Watkins, D. ; Torres, Jose V ; Berzofsky, J. A. ; Belyakov, I. M. ; Strober, W. ; Franchini, G. / Impairment of Gag-specific CD8+ T-cell function in mucosal and systemic compartments of simian immunodeficiency virus mac251- and simian-human immunodeficiency virus KU2-infected macaques. In: Journal of Virology. 2001 ; Vol. 75, No. 23. pp. 11483-11495.
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abstract = "The identification of several simian immunodeficiency virus mac251 (SIVmac251) cytotoxic T-lymphocyte epitopes recognized by CD8+ T cells of infected rhesus macaques carrying the Mamu-A*01 molecule and the use of peptide-major histocompatibility complex tetrameric complexes enable the study of the frequency, breadth, functionality, and distribution of virus-specific CD8+ T cells in the body. To begin to address these issues, we have performed a pilot study to measure the virus-specific CD8+ and CD4+ T-cell response in the blood, lymph nodes, spleen, and gastrointestinal lymphoid tissues of eight Mamu-A*01-positive macaques, six of those infected with SIVmac251 and two infected with the pathogenic simian-human immunodeficiency virus KU2. We focused on the analysis of the response to peptide p11C, C-M (Gag 181), since it was predominant in most tissues of all macaques. Five macaques restricted viral replication effectively, whereas the remaining three failed to control viremia and experienced a progressive loss of CD4+ T cells. The frequency of the Gag 181 (p11C, C→M) immunodominant response varied among different tissues of the same animal and in the same tissues from different animals. We found that the functionality of this virus-specific CD8+ T-cell population could not be assumed based on the ability to specifically bind to the Gag 181 tetramer, particularly in the mucosal tissues of some of the macaques infected by SIVmac251 that were progressing to disease. Overall, the functionality of CD8+ tetramer-binding T cells in tissues assessed by either measurement of cytolytic activity or the ability of these cells to produce gamma interferon or tumor necrosis factor alpha was low and was even lower in the mucosal tissue than in blood or spleen of some SIVmac251-infected animals that failed to control viremia. The data obtained in this pilot study lead to the hypothesis that disease progression may be associated with loss of virus-specific CD8+ T-cell function.",
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AU - Hel, Z.

AU - Nacsa, J.

AU - Kelsall, B.

AU - Tsai, W. P.

AU - Letvin, N.

AU - Parks, R. W.

AU - Tryniszewska, E.

AU - Picker, L.

AU - Lewis, M. G.

AU - Edghill-Smith, Y.

AU - Moniuszko, M.

AU - Pal, R.

AU - Stevceva, L.

AU - Altman, J. D.

AU - Allen, T. M.

AU - Watkins, D.

AU - Torres, Jose V

AU - Berzofsky, J. A.

AU - Belyakov, I. M.

AU - Strober, W.

AU - Franchini, G.

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