Functional heterogeneity of vaccine-induced CD8+ T cells

Vladia Monsurrò, Dirk Nagorsen, Ena Wang, Maurizio Provenzano, Mark E. Dudley, Steven A. Rosenberg, Francesco M. Marincola

Research output: Contribution to journalArticle

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Abstract

The functional status of circulating vaccine-induced, tumor-specific T cells has been questioned to explain their paradoxical inability to inhibit tumor growth. We enumerated with HLA-A*0201/peptide tetramers (tHLA) vaccine-elicited CD8+ T cell precursor frequency among PBMC in 13 patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100: 209-217(210 M) epitope. T cell precursor frequency increased from undetectable to 12,400 ± 3,600 × 106 CD8+ T cells after vaccination and appeared heterogeneous according to previously described functional subtypes: CD45RA+CD27+ (14 ± 2.6% of tHLA-staining T cells), naive; CD45RA-CD27+ (14 ± 3.2%), memory; CD45RA+CD27- (43 ± 6%), effector; and CD45RA-CD27- (30 ± 4.1%), memory/effector. The majority of tHLA+CD8+ T cells displayed an effector, CD27- phenotype (73%). However, few expressed perforin (17%). Epitope-specific in vitro stimulation (IVS) followed by 10-day expansion in IL-2 reversed this phenotype by increasing the number of perforin+ (84 ± 3.6%; by paired t test, p < 0.001) and CD27+ (from 28 to 67%; by paired t test, p = 0.01) tHLA+ T cells. This conversion probably represented a change in the functional status of tHLA+ T cells rather than a preferential expansion of a CD27+ (naive and/or memory) PBMC, because it was reproduced after IVS of a T cell clone bearing a classic effector phenotype (CD45RA+CD27-). These findings suggest that circulating vaccine-elicited T cells are not as functionally active as inferred by characterization of IVS-induced CTL. In addition, CD45RA/CD27 expression may be more informative about the status of activation of circulating T cells than their status of differentiation.

Original languageEnglish
Pages (from-to)5933-5942
Number of pages10
JournalJournal of Immunology
Volume168
Issue number11
Publication statusPublished - 1 Jun 2002
Externally publishedYes

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Vaccines
T-Lymphocytes
T-Lymphoid Precursor Cells
Perforin
Phenotype
Epitopes
Vaccination
Cancer Vaccines
Interleukin-2
Melanoma
Clone Cells
Staining and Labeling
Peptides
Growth
In Vitro Techniques
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

Monsurrò, V., Nagorsen, D., Wang, E., Provenzano, M., Dudley, M. E., Rosenberg, S. A., & Marincola, F. M. (2002). Functional heterogeneity of vaccine-induced CD8+ T cells. Journal of Immunology, 168(11), 5933-5942.

Functional heterogeneity of vaccine-induced CD8+ T cells. / Monsurrò, Vladia; Nagorsen, Dirk; Wang, Ena; Provenzano, Maurizio; Dudley, Mark E.; Rosenberg, Steven A.; Marincola, Francesco M.

In: Journal of Immunology, Vol. 168, No. 11, 01.06.2002, p. 5933-5942.

Research output: Contribution to journalArticle

Monsurrò, V, Nagorsen, D, Wang, E, Provenzano, M, Dudley, ME, Rosenberg, SA & Marincola, FM 2002, 'Functional heterogeneity of vaccine-induced CD8+ T cells', Journal of Immunology, vol. 168, no. 11, pp. 5933-5942.
Monsurrò V, Nagorsen D, Wang E, Provenzano M, Dudley ME, Rosenberg SA et al. Functional heterogeneity of vaccine-induced CD8+ T cells. Journal of Immunology. 2002 Jun 1;168(11):5933-5942.
Monsurrò, Vladia ; Nagorsen, Dirk ; Wang, Ena ; Provenzano, Maurizio ; Dudley, Mark E. ; Rosenberg, Steven A. ; Marincola, Francesco M. / Functional heterogeneity of vaccine-induced CD8+ T cells. In: Journal of Immunology. 2002 ; Vol. 168, No. 11. pp. 5933-5942.
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abstract = "The functional status of circulating vaccine-induced, tumor-specific T cells has been questioned to explain their paradoxical inability to inhibit tumor growth. We enumerated with HLA-A*0201/peptide tetramers (tHLA) vaccine-elicited CD8+ T cell precursor frequency among PBMC in 13 patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100: 209-217(210 M) epitope. T cell precursor frequency increased from undetectable to 12,400 ± 3,600 × 106 CD8+ T cells after vaccination and appeared heterogeneous according to previously described functional subtypes: CD45RA+CD27+ (14 ± 2.6{\%} of tHLA-staining T cells), naive; CD45RA-CD27+ (14 ± 3.2{\%}), memory; CD45RA+CD27- (43 ± 6{\%}), effector; and CD45RA-CD27- (30 ± 4.1{\%}), memory/effector. The majority of tHLA+CD8+ T cells displayed an effector, CD27- phenotype (73{\%}). However, few expressed perforin (17{\%}). Epitope-specific in vitro stimulation (IVS) followed by 10-day expansion in IL-2 reversed this phenotype by increasing the number of perforin+ (84 ± 3.6{\%}; by paired t test, p < 0.001) and CD27+ (from 28 to 67{\%}; by paired t test, p = 0.01) tHLA+ T cells. This conversion probably represented a change in the functional status of tHLA+ T cells rather than a preferential expansion of a CD27+ (naive and/or memory) PBMC, because it was reproduced after IVS of a T cell clone bearing a classic effector phenotype (CD45RA+CD27-). These findings suggest that circulating vaccine-elicited T cells are not as functionally active as inferred by characterization of IVS-induced CTL. In addition, CD45RA/CD27 expression may be more informative about the status of activation of circulating T cells than their status of differentiation.",
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