Visualization of polyoma virus-specific CD8+ T cells in vivo during infection and tumor rejection

Aron Lukacher, Janice M. Moser, Annette Hadley, John D. Altman

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

T cells are critical for clearing infection and preventing tumors induced by polyoma virus, a natural murine papovavirus. We previously identified the immunodominant epitope for polyoma virus-specific CTL in tumor-resistant H-2(k) mice as the D(k)restricted peptide, MT389-397, derived from the polyoma middle T oncoprotein. In this study, we developed tetrameric D(k) complexes containing the MT389-397 peptide to directly visualize and enumerate MT389-397-specific CTL during polyoma virus infection. We found that D(k)/MT389 tetramer+CD8+ T cells undergo a massive expansion during primary infection such that by day 7 postinfection these Ag-specific CD8+ T cells constitute ~20% of the total and ~40% of the activated CD8+ T cells in the spleen. This expansion of D(k)/MT389 tetramer+CD8+ T cells parallels the emergence of MT389-397-specific ex vivo cytolytic activity and clearance of polyoma virus. Notably, D(k)/MT389 tetramer+CD8+ T cells are maintained in memory at very high levels. The frequencies of D(k)/MT389 tetramer+CD8+ effector and memory T cells in vivo match those of CD8+ T cells producing intracellular IFN-γ after 6-h in vitro stimulation by MT389-397 peptide. Consistent with preferential Vβ6 expression by MT389-397-specific CD8+CTL lines and clones, D(k)/MT389 tetramer+CD8+ T cells exhibit biased expression of this Vβ gene segment. Finally, we show that D(k)/MT389 tetramer+CD8+ T cells efficiently infiltrate a polyoma tumor challenge to virus-immune mice. Taken together, these findings strongly implicate virus- induced MT389-397-specific CD8+ T cells as essential effectors in eliminating polyoma-infected and polyoma-transformed cells in vivo.

Original languageEnglish (US)
Pages (from-to)3369-3378
Number of pages10
JournalJournal of Immunology
Volume163
Issue number6
StatePublished - Sep 15 1999

Fingerprint

Polyomavirus
T-Lymphocytes
Infection
Neoplasms
Peptides
Rejection (Psychology)
Viruses
Immunodominant Epitopes
Oncogene Proteins
Virus Diseases
Spleen
Clone Cells

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Lukacher, Aron ; Moser, Janice M. ; Hadley, Annette ; Altman, John D. / Visualization of polyoma virus-specific CD8+ T cells in vivo during infection and tumor rejection. In: Journal of Immunology. 1999 ; Vol. 163, No. 6. pp. 3369-3378.
@article{6c78c29687714cc0a77194e491382211,
title = "Visualization of polyoma virus-specific CD8+ T cells in vivo during infection and tumor rejection",
abstract = "T cells are critical for clearing infection and preventing tumors induced by polyoma virus, a natural murine papovavirus. We previously identified the immunodominant epitope for polyoma virus-specific CTL in tumor-resistant H-2(k) mice as the D(k)restricted peptide, MT389-397, derived from the polyoma middle T oncoprotein. In this study, we developed tetrameric D(k) complexes containing the MT389-397 peptide to directly visualize and enumerate MT389-397-specific CTL during polyoma virus infection. We found that D(k)/MT389 tetramer+CD8+ T cells undergo a massive expansion during primary infection such that by day 7 postinfection these Ag-specific CD8+ T cells constitute ~20{\%} of the total and ~40{\%} of the activated CD8+ T cells in the spleen. This expansion of D(k)/MT389 tetramer+CD8+ T cells parallels the emergence of MT389-397-specific ex vivo cytolytic activity and clearance of polyoma virus. Notably, D(k)/MT389 tetramer+CD8+ T cells are maintained in memory at very high levels. The frequencies of D(k)/MT389 tetramer+CD8+ effector and memory T cells in vivo match those of CD8+ T cells producing intracellular IFN-γ after 6-h in vitro stimulation by MT389-397 peptide. Consistent with preferential Vβ6 expression by MT389-397-specific CD8+CTL lines and clones, D(k)/MT389 tetramer+CD8+ T cells exhibit biased expression of this Vβ gene segment. Finally, we show that D(k)/MT389 tetramer+CD8+ T cells efficiently infiltrate a polyoma tumor challenge to virus-immune mice. Taken together, these findings strongly implicate virus- induced MT389-397-specific CD8+ T cells as essential effectors in eliminating polyoma-infected and polyoma-transformed cells in vivo.",
author = "Aron Lukacher and Moser, {Janice M.} and Annette Hadley and Altman, {John D.}",
year = "1999",
month = "9",
day = "15",
language = "English (US)",
volume = "163",
pages = "3369--3378",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

Visualization of polyoma virus-specific CD8+ T cells in vivo during infection and tumor rejection. / Lukacher, Aron; Moser, Janice M.; Hadley, Annette; Altman, John D.

In: Journal of Immunology, Vol. 163, No. 6, 15.09.1999, p. 3369-3378.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Visualization of polyoma virus-specific CD8+ T cells in vivo during infection and tumor rejection

AU - Lukacher, Aron

AU - Moser, Janice M.

AU - Hadley, Annette

AU - Altman, John D.

PY - 1999/9/15

Y1 - 1999/9/15

N2 - T cells are critical for clearing infection and preventing tumors induced by polyoma virus, a natural murine papovavirus. We previously identified the immunodominant epitope for polyoma virus-specific CTL in tumor-resistant H-2(k) mice as the D(k)restricted peptide, MT389-397, derived from the polyoma middle T oncoprotein. In this study, we developed tetrameric D(k) complexes containing the MT389-397 peptide to directly visualize and enumerate MT389-397-specific CTL during polyoma virus infection. We found that D(k)/MT389 tetramer+CD8+ T cells undergo a massive expansion during primary infection such that by day 7 postinfection these Ag-specific CD8+ T cells constitute ~20% of the total and ~40% of the activated CD8+ T cells in the spleen. This expansion of D(k)/MT389 tetramer+CD8+ T cells parallels the emergence of MT389-397-specific ex vivo cytolytic activity and clearance of polyoma virus. Notably, D(k)/MT389 tetramer+CD8+ T cells are maintained in memory at very high levels. The frequencies of D(k)/MT389 tetramer+CD8+ effector and memory T cells in vivo match those of CD8+ T cells producing intracellular IFN-γ after 6-h in vitro stimulation by MT389-397 peptide. Consistent with preferential Vβ6 expression by MT389-397-specific CD8+CTL lines and clones, D(k)/MT389 tetramer+CD8+ T cells exhibit biased expression of this Vβ gene segment. Finally, we show that D(k)/MT389 tetramer+CD8+ T cells efficiently infiltrate a polyoma tumor challenge to virus-immune mice. Taken together, these findings strongly implicate virus- induced MT389-397-specific CD8+ T cells as essential effectors in eliminating polyoma-infected and polyoma-transformed cells in vivo.

AB - T cells are critical for clearing infection and preventing tumors induced by polyoma virus, a natural murine papovavirus. We previously identified the immunodominant epitope for polyoma virus-specific CTL in tumor-resistant H-2(k) mice as the D(k)restricted peptide, MT389-397, derived from the polyoma middle T oncoprotein. In this study, we developed tetrameric D(k) complexes containing the MT389-397 peptide to directly visualize and enumerate MT389-397-specific CTL during polyoma virus infection. We found that D(k)/MT389 tetramer+CD8+ T cells undergo a massive expansion during primary infection such that by day 7 postinfection these Ag-specific CD8+ T cells constitute ~20% of the total and ~40% of the activated CD8+ T cells in the spleen. This expansion of D(k)/MT389 tetramer+CD8+ T cells parallels the emergence of MT389-397-specific ex vivo cytolytic activity and clearance of polyoma virus. Notably, D(k)/MT389 tetramer+CD8+ T cells are maintained in memory at very high levels. The frequencies of D(k)/MT389 tetramer+CD8+ effector and memory T cells in vivo match those of CD8+ T cells producing intracellular IFN-γ after 6-h in vitro stimulation by MT389-397 peptide. Consistent with preferential Vβ6 expression by MT389-397-specific CD8+CTL lines and clones, D(k)/MT389 tetramer+CD8+ T cells exhibit biased expression of this Vβ gene segment. Finally, we show that D(k)/MT389 tetramer+CD8+ T cells efficiently infiltrate a polyoma tumor challenge to virus-immune mice. Taken together, these findings strongly implicate virus- induced MT389-397-specific CD8+ T cells as essential effectors in eliminating polyoma-infected and polyoma-transformed cells in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0033568287&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033568287&partnerID=8YFLogxK

M3 - Article

C2 - 10477607

AN - SCOPUS:0033568287

VL - 163

SP - 3369

EP - 3378

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -