Human CD8+ T cells expressing HLA-DR and CD28 show telomerase activity and are distinct from cytolytic effector T cells

Speiser, Daniel E.; Migliaccio, Marianna; Pittet, Mikaël J.; Valmori, Danila; Líénard, Danielle; Lejeune, Ferdy J.; Reichenbach, Patrick; Guillaume, Philippe; Lüscher, Immanuel F.; Cerottini, Jean‐Charles; Romero, Pedro

doi:10.1002/1521-4141(200102)31:2<459::aid-immu459>3.0.co;2-y

Cited by 50 publications

(41 citation statements)

References 37 publications

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“…In healthy donors, Melan-A-specific T cells are found at relatively high frequencies, even though they are not activated (i.e., they are CD45RA ϩ , CCR7 ϩ , CD28 ϩ , and HLA-DR Ϫ ) (17,29). These cells are generally considered naive and resting, and our analysis showed that most were 2B4 negative (Fig.…”

Section: Ag-specific T Cells Show Characteristic 2b4 Expression Depenmentioning

confidence: 72%

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The Activatory Receptor 2B4 Is Expressed In Vivo by Human CD8+ Effector αβ T Cells

Speiser

Colonna

Ayyoub

et al. 2001

The Journal of Immunology

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The membrane receptor 2B4 is a CD2 family member that is involved in lymphocyte activation. A fraction of human CD8+ αβ T cells up-regulate 2B4 in vivo, and here we demonstrate that this correlates with the acquisition of effector cell properties such as granzyme B and perforin expression, rapid IFN-γ production, and down-regulation of the lymph node homing chemokine receptor CCR7. In PBLs from healthy donors, cytomegalovirus-specific effector T cells were 2B4 positive, whereas naive melanoma Ag (Melan-A/melanoma Ag recognized by T cells-1)-specific T cells were 2B4 negative. In melanoma patients, Melan-A-specific T cells up-regulated 2B4 in parallel with in vivo differentiation. This occurred in PBLs after vaccination with Melan-A peptides and in tumor-infiltrated lymph nodes, likely through disease-associated activation of Melan-A-specific T cells. Thus, 2B4 expression correlates with CD8+ T cell differentiation in vivo.

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Section: Ag-specific T Cells Show Characteristic 2b4 Expression Depenmentioning

confidence: 72%

“…Immunotherapy was given i.m. at weeks 0, 4, 8, and 12 (17). SB-AS2 was provided by SmithKline Beecham (Rixensart, Belgium).…”

Section: Healthy Donors and Melanoma Patientsmentioning

confidence: 99%

The Activatory Receptor 2B4 Is Expressed In Vivo by Human CD8+ Effector αβ T Cells

Speiser

Colonna

Ayyoub

et al. 2001

The Journal of Immunology

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“…However, in our study the density of tumor-infiltrating CD8+ T cells was not related to patient prognosis. Further studies investigating organ-specific immune responses or the proportion of activated tumor-infiltrating CD8+ T cells 30) after CRT are needed. Changes in the tumor-infiltrating T cell subpopulation's density throughout the course of CRT, if present, would be important information to assess therapeutic response.…”

Section: Discussionmentioning

confidence: 99%

Density of Tumor-Infiltrating FOXP3+ T Cells as a Response Marker for Induction Chemoradiotherapy and a Potential Prognostic Factor in Patients Treated with Trimodality Therapy for Locally Advanced Non-Small Cell Lung Cancer

Tao¹,

Shien

Soh

et al. 2014

ATCS

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“…To rule out functional unresponsiveness (17), we assessed the capacity of Melan-A-specific CD8 ϩ T cells to secrete IFN-␥ by using the mentioned IFN-␥ secretion assay in three melanoma patients with different clinical conditions. Patient LAU 465 did not receive any therapy at the time of blood collection; patient LAU 156 was treated with IFN-␣ and developed vitiligo 5 years before blood collection; patient LAU 337 received repeated vaccination with Melan-A 26 -35 peptide plus SBA-S2 adjuvant and concomitantly developed a systemic CD8 ϩ T cell response against Melan-A 26 -35 (18,28 (Fig. 6B).…”

Section: Analysis Of Melan-a-specific Cd8 ϩ T Cells In Melanoma Patientsmentioning

confidence: 99%

Ex Vivo IFN-γ Secretion by Circulating CD8 T Lymphocytes: Implications of a Novel Approach for T Cell Monitoring in Infectious and Malignant Diseases

Pittet¹,

Zippelius²,

Speiser³

et al. 2001

The Journal of Immunology

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127

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To elucidate the functional heterogeneity of Ag-specific T lymphocyte populations, we combined labeling of lymphocytes with MHC/peptide tetramers and a cell surface affinity matrix for IFN-γ. Magnetic cell sorting of IFN-γ-positive lymphocytes allowed the selective enrichment and identification of live Ag-specific cytokine-secreting cells by flow cytometry. Naive, memory, and effector Ag-specific populations were evaluated in healthy HLA-A2 individuals. Significant fractions of influenza- and CMV-specific cells secreted IFN-γ upon challenge with cognate peptide, consistent with an effector/memory status. The sensitivity of the approach allowed the detection of significant numbers of CMV-specific IFN-γ-secreting cells ex vivo (i.e., without Ag stimulation). This was not apparent when using previously described assays, namely, ELISPOT or intracellular IFN-γ staining (cytospot). CD8+ T cells specific for the melamoma-associated Ag Melan-A/MART-1 did not produce IFN-γ upon challenge with cognate peptide, reminiscent with their naive functional state in healthy individuals. In contrast, CD45RAlow Melan-A/MART-1 tumor-specific cells from three of three melanoma patients presented levels of activity similar to those found for influenza- or CMV virus-specific lymphocytes, compatible with a functional differentiation into competent effector/memory T lymphocytes in vivo. Notably, a sizable fraction of Melan-A/MART-1-specific cells from a patient secreted IFN-γ ex vivo following peptide-based vaccination. Thus, the high sensitivity of the assay provides a valuable tool to monitor effector T cell responses in different clinical situations.

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Human CD8+ T cells expressing HLA-DR and CD28 show telomerase activity and are distinct from cytolytic effector T cells

Cited by 50 publications

References 37 publications

The Activatory Receptor 2B4 Is Expressed In Vivo by Human CD8+ Effector αβ T Cells

The Activatory Receptor 2B4 Is Expressed In Vivo by Human CD8+ Effector αβ T Cells

Density of Tumor-Infiltrating FOXP3+ T Cells as a Response Marker for Induction Chemoradiotherapy and a Potential Prognostic Factor in Patients Treated with Trimodality Therapy for Locally Advanced Non-Small Cell Lung Cancer

Ex Vivo IFN-γ Secretion by Circulating CD8 T Lymphocytes: Implications of a Novel Approach for T Cell Monitoring in Infectious and Malignant Diseases

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