Independence of granzyme B secretion and interferon-γ production during acute simian immunodeficiency virus infection

Sandra A. Calarota, Miguel Otero, Tara M. Robinson, Anlan Dai, Mark G. Lewis, Jean D. Boyer, David B. Weiner

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background. Quantification of interferon (IFN)-γ by enzyme-linked immunospot (ELISPOT) assay is currently used as a surrogate measurement of cytotoxic T lymphocyte (CTL) activity in nonhuman primates, particularly in simian immunodeficiency virus (SIV) models. Given that noncytotoxic cells and natural killer cells can also release IFN-γ, quantification of granzyme B (GrB), a molecule secreted predominantly by activated CD8 + T cells, may represent an additional surrogate measurement of CTL activity. Methods. We evaluated, by ELISPOT assay, GrB activity in response to 3 overlapping SIV Gag peptide pools in 18 rhesus macaques with acute SIV mac251 infection and analyzed its correlation with IFN-γ ELISPOT responses and plasma viral load. Results. SIV Gag-specific GrB activity increased from 3.9- to 14.4-fold after infection, compared with that observed before infection. GrB secretion did not correlate directly with IFN-γ production. Importantly, SIV Gag-specific IFN-γ production was negatively correlated with plasma viral load, whereas GrB activity was not. However, the peak of GrB activity coincided with the lowest plasma viral load detected after infection, whereas the magnitude of IFN-γ production was 1.8-fold lower than the GrB response; these results illustrate that the responses differ. Conclusion. Our data support the concept that the GrB and IFN-γ ELISPOT assays measure immune responses in different immune-cell populations with unique specificities.

Original languageEnglish
Pages (from-to)1441-1450
Number of pages10
JournalJournal of Infectious Diseases
Volume193
Issue number10
DOIs
Publication statusPublished - May 15 2006

Fingerprint

Granzymes
Simian Immunodeficiency Virus
Virus Diseases
Interferons
Enzyme-Linked Immunospot Assay
Viral Load
Cytotoxic T-Lymphocytes
Infection
Macaca mulatta
Natural Killer Cells
Primates
T-Lymphocytes
Peptides
Enzymes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Calarota, S. A., Otero, M., Robinson, T. M., Dai, A., Lewis, M. G., Boyer, J. D., & Weiner, D. B. (2006). Independence of granzyme B secretion and interferon-γ production during acute simian immunodeficiency virus infection. Journal of Infectious Diseases, 193(10), 1441-1450. https://doi.org/10.1086/503364

Independence of granzyme B secretion and interferon-γ production during acute simian immunodeficiency virus infection. / Calarota, Sandra A.; Otero, Miguel; Robinson, Tara M.; Dai, Anlan; Lewis, Mark G.; Boyer, Jean D.; Weiner, David B.

In: Journal of Infectious Diseases, Vol. 193, No. 10, 15.05.2006, p. 1441-1450.

Research output: Contribution to journalArticle

Calarota, SA, Otero, M, Robinson, TM, Dai, A, Lewis, MG, Boyer, JD & Weiner, DB 2006, 'Independence of granzyme B secretion and interferon-γ production during acute simian immunodeficiency virus infection', Journal of Infectious Diseases, vol. 193, no. 10, pp. 1441-1450. https://doi.org/10.1086/503364
Calarota, Sandra A. ; Otero, Miguel ; Robinson, Tara M. ; Dai, Anlan ; Lewis, Mark G. ; Boyer, Jean D. ; Weiner, David B. / Independence of granzyme B secretion and interferon-γ production during acute simian immunodeficiency virus infection. In: Journal of Infectious Diseases. 2006 ; Vol. 193, No. 10. pp. 1441-1450.
@article{7a7d2c210c974bab98b9bc370473506e,
title = "Independence of granzyme B secretion and interferon-γ production during acute simian immunodeficiency virus infection",
abstract = "Background. Quantification of interferon (IFN)-γ by enzyme-linked immunospot (ELISPOT) assay is currently used as a surrogate measurement of cytotoxic T lymphocyte (CTL) activity in nonhuman primates, particularly in simian immunodeficiency virus (SIV) models. Given that noncytotoxic cells and natural killer cells can also release IFN-γ, quantification of granzyme B (GrB), a molecule secreted predominantly by activated CD8 + T cells, may represent an additional surrogate measurement of CTL activity. Methods. We evaluated, by ELISPOT assay, GrB activity in response to 3 overlapping SIV Gag peptide pools in 18 rhesus macaques with acute SIV mac251 infection and analyzed its correlation with IFN-γ ELISPOT responses and plasma viral load. Results. SIV Gag-specific GrB activity increased from 3.9- to 14.4-fold after infection, compared with that observed before infection. GrB secretion did not correlate directly with IFN-γ production. Importantly, SIV Gag-specific IFN-γ production was negatively correlated with plasma viral load, whereas GrB activity was not. However, the peak of GrB activity coincided with the lowest plasma viral load detected after infection, whereas the magnitude of IFN-γ production was 1.8-fold lower than the GrB response; these results illustrate that the responses differ. Conclusion. Our data support the concept that the GrB and IFN-γ ELISPOT assays measure immune responses in different immune-cell populations with unique specificities.",
author = "Calarota, {Sandra A.} and Miguel Otero and Robinson, {Tara M.} and Anlan Dai and Lewis, {Mark G.} and Boyer, {Jean D.} and Weiner, {David B.}",
year = "2006",
month = "5",
day = "15",
doi = "10.1086/503364",
language = "English",
volume = "193",
pages = "1441--1450",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - Independence of granzyme B secretion and interferon-γ production during acute simian immunodeficiency virus infection

AU - Calarota, Sandra A.

AU - Otero, Miguel

AU - Robinson, Tara M.

AU - Dai, Anlan

AU - Lewis, Mark G.

AU - Boyer, Jean D.

AU - Weiner, David B.

PY - 2006/5/15

Y1 - 2006/5/15

N2 - Background. Quantification of interferon (IFN)-γ by enzyme-linked immunospot (ELISPOT) assay is currently used as a surrogate measurement of cytotoxic T lymphocyte (CTL) activity in nonhuman primates, particularly in simian immunodeficiency virus (SIV) models. Given that noncytotoxic cells and natural killer cells can also release IFN-γ, quantification of granzyme B (GrB), a molecule secreted predominantly by activated CD8 + T cells, may represent an additional surrogate measurement of CTL activity. Methods. We evaluated, by ELISPOT assay, GrB activity in response to 3 overlapping SIV Gag peptide pools in 18 rhesus macaques with acute SIV mac251 infection and analyzed its correlation with IFN-γ ELISPOT responses and plasma viral load. Results. SIV Gag-specific GrB activity increased from 3.9- to 14.4-fold after infection, compared with that observed before infection. GrB secretion did not correlate directly with IFN-γ production. Importantly, SIV Gag-specific IFN-γ production was negatively correlated with plasma viral load, whereas GrB activity was not. However, the peak of GrB activity coincided with the lowest plasma viral load detected after infection, whereas the magnitude of IFN-γ production was 1.8-fold lower than the GrB response; these results illustrate that the responses differ. Conclusion. Our data support the concept that the GrB and IFN-γ ELISPOT assays measure immune responses in different immune-cell populations with unique specificities.

AB - Background. Quantification of interferon (IFN)-γ by enzyme-linked immunospot (ELISPOT) assay is currently used as a surrogate measurement of cytotoxic T lymphocyte (CTL) activity in nonhuman primates, particularly in simian immunodeficiency virus (SIV) models. Given that noncytotoxic cells and natural killer cells can also release IFN-γ, quantification of granzyme B (GrB), a molecule secreted predominantly by activated CD8 + T cells, may represent an additional surrogate measurement of CTL activity. Methods. We evaluated, by ELISPOT assay, GrB activity in response to 3 overlapping SIV Gag peptide pools in 18 rhesus macaques with acute SIV mac251 infection and analyzed its correlation with IFN-γ ELISPOT responses and plasma viral load. Results. SIV Gag-specific GrB activity increased from 3.9- to 14.4-fold after infection, compared with that observed before infection. GrB secretion did not correlate directly with IFN-γ production. Importantly, SIV Gag-specific IFN-γ production was negatively correlated with plasma viral load, whereas GrB activity was not. However, the peak of GrB activity coincided with the lowest plasma viral load detected after infection, whereas the magnitude of IFN-γ production was 1.8-fold lower than the GrB response; these results illustrate that the responses differ. Conclusion. Our data support the concept that the GrB and IFN-γ ELISPOT assays measure immune responses in different immune-cell populations with unique specificities.

UR - http://www.scopus.com/inward/record.url?scp=33646364807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646364807&partnerID=8YFLogxK

U2 - 10.1086/503364

DO - 10.1086/503364

M3 - Article

VL - 193

SP - 1441

EP - 1450

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 10

ER -