Status of activation of circulating vaccine-elicited CD8+ T cells

M. B. Nielsen, V. Monsurro, S. A. Migueles, E. Wang, A. Perez-Diez, H. Lee, U. Kammula, S. A. Rosenberg, F. M. Marincola

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Selective blunting of the status of activation of circulating tumor- specific T cells was invoked to explain their paradoxical coexistence with unhampered tumor growth. By analogy, lack of tumor regression in the face of observable melanoma vaccine-induced T cell responses might be attributed to their status of activation. We enumerated with HLA-A *0201/peptide tetramers (tHLA) vaccine-elicited T cell precursor frequency directly in PBMC of patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209-217(210 M) epitope (g209-2 M). Furthermore, we tested by intracellular (IC)-FACS analysis and quantitative real-time PCR (qRT-PCR) the ability of postvaccination PBMC to produce cytokine in response to challenge with vaccine-related epitopes or vaccine-matched (HLA-A *0201) melanoma cells. Vaccine-induced enhancement of T cell precursor frequency could be detected with tHLA in PBMC from six of eight patients studied at frequencies ranging between 0.3 and 2.3% of the total CD8+ population. Stimulation with vaccine-related epitopes induced IFN-γ expression detectable by IC-FACS or qRT-PCR, respectively, in five and six of these patients. Furthermore, down- regulation of tHLA staining was noted upon cognate stimulation that could be utilized as an additional marker of T cell responsiveness. Finally, we observed in six patients an enhancement of reactivity against vaccine-matched tumor targets that was partly independent of documented vaccine-specific immune responses. A strong correlation was noted between tHLA staining of postvaccination PBMC and IFN-γ expression by the same samples upon vaccine- relevant stimulation and assessed either by IC-FACS or qRT-PCR. Thus, blunting of the status of T cell activation on itself cannot easily explain the lack of clinical responses observed with vaccination.

Original languageEnglish
Pages (from-to)2287-2296
Number of pages10
JournalJournal of Immunology
Volume165
Issue number4
Publication statusPublished - 15 Aug 2000
Externally publishedYes

Fingerprint

Vaccines
T-Lymphocytes
T-Lymphoid Precursor Cells
Real-Time Polymerase Chain Reaction
Epitopes
Melanoma
Vaccination
Staining and Labeling
Neoplasms
Cancer Vaccines
Down-Regulation
Cytokines
Peptides
Growth
Population
HLA-A*02:01 antigen

ASJC Scopus subject areas

  • Immunology

Cite this

Nielsen, M. B., Monsurro, V., Migueles, S. A., Wang, E., Perez-Diez, A., Lee, H., ... Marincola, F. M. (2000). Status of activation of circulating vaccine-elicited CD8+ T cells. Journal of Immunology, 165(4), 2287-2296.

Status of activation of circulating vaccine-elicited CD8+ T cells. / Nielsen, M. B.; Monsurro, V.; Migueles, S. A.; Wang, E.; Perez-Diez, A.; Lee, H.; Kammula, U.; Rosenberg, S. A.; Marincola, F. M.

In: Journal of Immunology, Vol. 165, No. 4, 15.08.2000, p. 2287-2296.

Research output: Contribution to journalArticle

Nielsen, MB, Monsurro, V, Migueles, SA, Wang, E, Perez-Diez, A, Lee, H, Kammula, U, Rosenberg, SA & Marincola, FM 2000, 'Status of activation of circulating vaccine-elicited CD8+ T cells', Journal of Immunology, vol. 165, no. 4, pp. 2287-2296.
Nielsen MB, Monsurro V, Migueles SA, Wang E, Perez-Diez A, Lee H et al. Status of activation of circulating vaccine-elicited CD8+ T cells. Journal of Immunology. 2000 Aug 15;165(4):2287-2296.
Nielsen, M. B. ; Monsurro, V. ; Migueles, S. A. ; Wang, E. ; Perez-Diez, A. ; Lee, H. ; Kammula, U. ; Rosenberg, S. A. ; Marincola, F. M. / Status of activation of circulating vaccine-elicited CD8+ T cells. In: Journal of Immunology. 2000 ; Vol. 165, No. 4. pp. 2287-2296.
@article{4612fb77a17e48a4a4dec7710a313440,
title = "Status of activation of circulating vaccine-elicited CD8+ T cells",
abstract = "Selective blunting of the status of activation of circulating tumor- specific T cells was invoked to explain their paradoxical coexistence with unhampered tumor growth. By analogy, lack of tumor regression in the face of observable melanoma vaccine-induced T cell responses might be attributed to their status of activation. We enumerated with HLA-A *0201/peptide tetramers (tHLA) vaccine-elicited T cell precursor frequency directly in PBMC of patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209-217(210 M) epitope (g209-2 M). Furthermore, we tested by intracellular (IC)-FACS analysis and quantitative real-time PCR (qRT-PCR) the ability of postvaccination PBMC to produce cytokine in response to challenge with vaccine-related epitopes or vaccine-matched (HLA-A *0201) melanoma cells. Vaccine-induced enhancement of T cell precursor frequency could be detected with tHLA in PBMC from six of eight patients studied at frequencies ranging between 0.3 and 2.3{\%} of the total CD8+ population. Stimulation with vaccine-related epitopes induced IFN-γ expression detectable by IC-FACS or qRT-PCR, respectively, in five and six of these patients. Furthermore, down- regulation of tHLA staining was noted upon cognate stimulation that could be utilized as an additional marker of T cell responsiveness. Finally, we observed in six patients an enhancement of reactivity against vaccine-matched tumor targets that was partly independent of documented vaccine-specific immune responses. A strong correlation was noted between tHLA staining of postvaccination PBMC and IFN-γ expression by the same samples upon vaccine- relevant stimulation and assessed either by IC-FACS or qRT-PCR. Thus, blunting of the status of T cell activation on itself cannot easily explain the lack of clinical responses observed with vaccination.",
author = "Nielsen, {M. B.} and V. Monsurro and Migueles, {S. A.} and E. Wang and A. Perez-Diez and H. Lee and U. Kammula and Rosenberg, {S. A.} and Marincola, {F. M.}",
year = "2000",
month = "8",
day = "15",
language = "English",
volume = "165",
pages = "2287--2296",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Status of activation of circulating vaccine-elicited CD8+ T cells

AU - Nielsen, M. B.

AU - Monsurro, V.

AU - Migueles, S. A.

AU - Wang, E.

AU - Perez-Diez, A.

AU - Lee, H.

AU - Kammula, U.

AU - Rosenberg, S. A.

AU - Marincola, F. M.

PY - 2000/8/15

Y1 - 2000/8/15

N2 - Selective blunting of the status of activation of circulating tumor- specific T cells was invoked to explain their paradoxical coexistence with unhampered tumor growth. By analogy, lack of tumor regression in the face of observable melanoma vaccine-induced T cell responses might be attributed to their status of activation. We enumerated with HLA-A *0201/peptide tetramers (tHLA) vaccine-elicited T cell precursor frequency directly in PBMC of patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209-217(210 M) epitope (g209-2 M). Furthermore, we tested by intracellular (IC)-FACS analysis and quantitative real-time PCR (qRT-PCR) the ability of postvaccination PBMC to produce cytokine in response to challenge with vaccine-related epitopes or vaccine-matched (HLA-A *0201) melanoma cells. Vaccine-induced enhancement of T cell precursor frequency could be detected with tHLA in PBMC from six of eight patients studied at frequencies ranging between 0.3 and 2.3% of the total CD8+ population. Stimulation with vaccine-related epitopes induced IFN-γ expression detectable by IC-FACS or qRT-PCR, respectively, in five and six of these patients. Furthermore, down- regulation of tHLA staining was noted upon cognate stimulation that could be utilized as an additional marker of T cell responsiveness. Finally, we observed in six patients an enhancement of reactivity against vaccine-matched tumor targets that was partly independent of documented vaccine-specific immune responses. A strong correlation was noted between tHLA staining of postvaccination PBMC and IFN-γ expression by the same samples upon vaccine- relevant stimulation and assessed either by IC-FACS or qRT-PCR. Thus, blunting of the status of T cell activation on itself cannot easily explain the lack of clinical responses observed with vaccination.

AB - Selective blunting of the status of activation of circulating tumor- specific T cells was invoked to explain their paradoxical coexistence with unhampered tumor growth. By analogy, lack of tumor regression in the face of observable melanoma vaccine-induced T cell responses might be attributed to their status of activation. We enumerated with HLA-A *0201/peptide tetramers (tHLA) vaccine-elicited T cell precursor frequency directly in PBMC of patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209-217(210 M) epitope (g209-2 M). Furthermore, we tested by intracellular (IC)-FACS analysis and quantitative real-time PCR (qRT-PCR) the ability of postvaccination PBMC to produce cytokine in response to challenge with vaccine-related epitopes or vaccine-matched (HLA-A *0201) melanoma cells. Vaccine-induced enhancement of T cell precursor frequency could be detected with tHLA in PBMC from six of eight patients studied at frequencies ranging between 0.3 and 2.3% of the total CD8+ population. Stimulation with vaccine-related epitopes induced IFN-γ expression detectable by IC-FACS or qRT-PCR, respectively, in five and six of these patients. Furthermore, down- regulation of tHLA staining was noted upon cognate stimulation that could be utilized as an additional marker of T cell responsiveness. Finally, we observed in six patients an enhancement of reactivity against vaccine-matched tumor targets that was partly independent of documented vaccine-specific immune responses. A strong correlation was noted between tHLA staining of postvaccination PBMC and IFN-γ expression by the same samples upon vaccine- relevant stimulation and assessed either by IC-FACS or qRT-PCR. Thus, blunting of the status of T cell activation on itself cannot easily explain the lack of clinical responses observed with vaccination.

UR - http://www.scopus.com/inward/record.url?scp=0034662982&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034662982&partnerID=8YFLogxK

M3 - Article

C2 - 10925318

AN - SCOPUS:0034662982

VL - 165

SP - 2287

EP - 2296

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -