Diminished Production of Interleukin 2 and Gamma-Interferon by Cloned «T» Cells from Patients with the Acquired Immunodeficiency Syndrome (AIDS)

1987 ◽  
Vol 73 (3) ◽  
pp. 273-278 ◽  
Author(s):  
Enrico Maggi ◽  
Donatella Macchia ◽  
Paola Parronchi ◽  
Domenico Milo ◽  
Sergio Romagnani
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Immune Deficiency Syndrome ◽  
Gamma Interferon ◽  
Aids Patients ◽  
T Cell Clones ◽  
Cell Clones ◽  
The Mean ◽  
Mean Concentration

A total of 76 T-cell clones established from peripheral blood (PB) of 2 patients with the acquired immune deficiency syndrome (AIDS) and of 141 T-cell clones established from PB of 3 normal donors were compared for their ability to produce interleukin 2 (IL-2) and gamma-interferon (γ-IFN). Twenty-seven clones from AIDS patients and 85 clones from controls expressed the CD4 phenotype, whereas 49 clones from AIDS patients and 56 clones from controls expressed the CD8 phenotype. There were no significant differences in the proportions of IL-2-producing CD4 T-cell clones established from PB of patients with AIDS and controls, but the mean concentration of IL-2 produced by CD4 clones from AIDS patients was significantly lower than that produced by CD4 clones from controls. Both the proportion of γ-IFN-producing CD4 clones and the mean concentration of γ-IFN produced by CD4 clones were significantly lower in AIDS patients than in controls. In contrast, there were no differences between AIDS patients and normal individuals in the proportion of IL-2- or Y-IFN-producing CD8 clones, or in the mean concentration of IL-2 and v-IFN produced by CD8 clones. These data suggest that the reduced ability of PB T-cells from patients with AIDS to produce IL-2 and v-IFN is not simply due to altered proportions or numbers of T-cell sub-populations, but also reflects intrinsic abnormalities of individual CD4 T lymphocytes.

scholarly journals Mobilization of pre-existing polyclonal T cells specific to neoantigens but not self-antigens during treatment of a patient with melanoma with bempegaldesleukin and nivolumab

2020 ◽  
Vol 8 (2) ◽  
pp. e001591
Author(s):  
Joshua R Veatch ◽  
Naina Singhi ◽  
Brenda Jesernig ◽  
Kelly G Paulson ◽  
Jonathan Zalevsky ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Immune Checkpoint Blockade ◽  
Tumor Rejection ◽  
T Cell Clones ◽  
Cell Clones ◽  
Self Antigen ◽  
Self Antigens

T cells that recognize self-antigens and mutated neoantigens are thought to mediate antitumor activity of immune checkpoint blockade (ICB) in melanoma. Few studies have analyzed self and neoantigen-specific T cell responses in patients responding to ICB. Here, we report a patient with metastatic melanoma who had a durable clinical response after treatment with the programmed cell death protein 1 inhibitor, nivolumab, combined with the first-in-class CD122-preferential interleukin-2 pathway agonist, bempegaldesleukin (BEMPEG, NKTR-214). We used a combination of antigen-specific T cell expansion and measurement of interferon-γ secretion to identify multiple CD4+ and CD8+ T cell clones specific for neoantigens, lineage-specific antigens and cancer testis antigens in blood and tumor from this patient prior to and after therapy. Polyclonal CD4+ and CD8+ T cells specific to multiple neoantigens but not self-antigens were highly enriched in pretreatment tumor compared with peripheral blood. Neoantigen, but not self-antigen-specific T cell clones expanded in frequency in the blood during successful treatment. There was evidence of dramatic immune infiltration into the tumor on treatment, and a modest increase in the relative frequency of intratumoral neoantigen-specific T cells. These observations suggest that diverse CD8+ and CD4+ T cell clones specific for neoantigens present in tumor before treatment had a greater role in immune tumor rejection as compared with self-antigen-specific T cells in this patient. Trial registration number: NCT02983045.

Analysis of T Cell Cloanlity of Ph+ Acute Lymphoblastic Leukemia with Chronic Gvhd in Continuous Remission after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3941-3941
Author(s):  
Xiuli Wu ◽  
Qifa Liu ◽  
Yangqiu Li ◽  
Shaohua Chen ◽  
Xuan Du ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Rt Pcr ◽  
Hematopoietic Stem ◽  
Blood Samples ◽  
T Cell Clones ◽  
Cell Clones ◽  
The Mean

Abstract Chronic graft-versus-host disease (cGVHD) is one of the major complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, recent study suggested that the presence of cGVHD might reduce the risk of relapse in Ph+ acute lymphoblastic leukemia (ALL) after allo-HSCT. GVHD is mediated by proliferation of special T-cell clones, we analyzed the T cell receptor (TCR) Vβ repertoire and cloanlity in Ph+ ALL patients undergone cGVHD after allo-HSCT in order to find the special T-cell clones associated with continuous remission. Allogeneic transplantations were performed in the first complete remission (CR) (6 ALLP190+ patients). The numbers of BCR-ABL copies in peripheral blood samples were assessed with the real-time quantitative RT-PCR (RQ-PCR) test at diagnosis, and every month after HSCT. The quantity of BCR-ABL transcript was normalized for normal ABL expression and the result was expressed as the ratio of BCR-ABL copies to ABL copies. With monitoring BCR-ABL copies of 6 BCR-ABLP190+ ALL patients after HSCT (the mean ratio of BCR-ABLP190/ABL at diagnose was 0.41 ± 0.39%), we found that 4 patients with extensive cutancous cGVHD had no evidence of leukemia recurrence, and the BCRABL transcripts of patients with cGVHD were remaining 0 copy, while 2 patients without cGVHD relapsed (the mean ratio of BCR-ABLP190/ABL was 7.56 ± 2.49%) and even dead within six months of HSCT. The expression and cloanlity analysis of TCR Vβ repertoire was detected in peripheral blood samples from patients with cGVHD by RT-PCR and genescan technique. TCR Vβ repertoires with polyclonal pattern were identified in normal controls and donor groups. However, the skew expression pattern of TCR Vβ repertoire could be detected in patients with cGVHD even more than 1 year after allo-HSCT. Among the 24 Vβ subfamilies, there were only 11~17 Vβ subfamilies expressed in cGVHD patients. Oligoclonal or monoclonal expanded T cells were identified in TCR Vβ 1, 2, 3, 7, 8, 12, 14, 16~20, 22 and 23 subfamilies in 4 ALL patients (BCR-ABLP190 remission) with cGVHD. As a contrast, oligoclonal or monoclonal expanded T cells were identified in TCR Vβ 2, 7, 8, 14, 17, 20, and 22 subfamilies in 2 chronic myeloid leukemia patients (BCR-ABLP210 remission) with cGVHD. In conclusion, the predominant usage and clonal expansion of TCR Vβ subfamily T cells could be found in Ph+ ALL patients with cGVHD and these groups of specific T-cell clones (Vβ 1, 3, 12, 16, 18, 19 and 23) were potentially associated with cGVHD in ALL and might be responsible for maintaining CR in Ph+ ALL patients after allo-HSCT. Research Funding.

scholarly journals Ex Vivo Monitoring of Antigen-Specific CD4+ T Cells after Recall Immunization with Tetanus Toxoid

2007 ◽  
Vol 14 (9) ◽  
pp. 1108-1116 ◽  
Author(s):  
Catherine Barbey ◽  
Estelle Pradervand ◽  
Nathalie Barbier ◽  
François Spertini
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Tetanus Toxoid ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Effector Memory ◽  
Specific Response ◽  
T Cell Clones ◽  
Cell Clones

ABSTRACT To monitor antigen-specific CD4+ T cells during a recall immune response to tetanus toxoid (TT), a sequential analysis including ex vivo phenotyping and cytokine flow cytometry, followed by cloning and T-cell-receptor (TCR) spectratyping of cytokine-positive CD4+ T cells, was performed. Grossly, twice as many TT-specific CD4+ T-cell clones, ex vivo derived from the CCR7+/− CD69+ interleukin-2-positive (IL-2+) CD4+ subsets, belonged to the central memory (TCM; CD62L+ CD27+ CCR7+) compared to the effector memory population (TEM; CD62L− CD27− CCR7−). After the boost, a predominant expansion of the TCM population was observed with more limited variations of the TEM population. TCR beta-chain-variable region (BV) spectratyping and sequencing confirmed a large concordance between most frequently expressed BV TCR-CDR3 from ex vivo-sorted CCR7+/− CD69+ IL-2+ CD4+ subsets and BV usage of in vitro-derived TT-specific CD4+ T-cell clones, further demonstrating the highly polyclonal but stable character of the specific recall response to TT. Taken together, ex vivo flow cytometry analysis focused on the CCR7+/− CD69+ IL-2+ CD4+ subsets appears to target the bulk of antigen-specific T cells and to reach an analytical power sufficient to adequately delineate in field trials the profile of the antigen-specific response to vaccine.

scholarly journals A novel subset of CD2-, CD3/T cell receptor alpha/beta+ human peripheral blood T cells. Phenotypic and functional characterization of interleukin 2-dependent CD2-CD3+ T cell clones.

1989 ◽  
Vol 170 (2) ◽  
pp. 559-569 ◽  
Author(s):  
D Kabelitz ◽  
P Conradt ◽  
S Schondelmaier ◽  
H Wagner ◽  
R Haars
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Sheep Erythrocyte ◽  
Interleukin 2 ◽  
Normal Peripheral Blood ◽  
T Cell Clones ◽  
Cell Clones ◽  
Alpha Beta ◽  
A Minor

It is generally believed that CD2 (T11, sheep erythrocyte receptor) is expressed on all human T cells. In the present study we have identified and characterized a minor subset of CD2- CD3/TCR alpha/beta+ T cells in the peripheral blood of healthy individuals. CD2-CD3+ T cells were enriched in PBMC depleted of plastic-adherent macrophages, E-rosetting (i.e., CD2+) T cells and surface Ig+ B cells. CD2-CD3+ T cells accounted for 0.1-0.8% of PBMC in six individuals. IL-2-dependent long-term clones of CD2-CD3+ T cells neither reacted with a panel of anti-CD2 mAbs nor expressed detectable levels of CD2 mRNA by Northern blot analysis. These clones, however, expressed a full-length TCR C beta mRNA and reacted with mAbs against TCR-alpha/beta, CD3, and CD4, and thus were mature T cells. CD2-CD3/TCR+ T cell clones could be triggered into proliferation, IL-2 production, and cytotoxic effector activity by anti-CD3 and anti-TCR mAbs. We conclude that (a) a minor subset of CD2-, CD3/TCR-alpha/beta+ T cells is present in normal peripheral blood; and (b) expression of CD2 at the level of protein and/or mRNA is not required for T cell signaling via the CD3/TCR molecular complex.

scholarly journals Control of Leishmania infantum Infection Is Associated with CD8+ and Gamma Interferon- and Interleukin-5-Producing CD4+ Antigen-Specific T Cells

1999 ◽  
Vol 67 (11) ◽  
pp. 5559-5566 ◽  
Author(s):  
Charles Mary ◽  
Valérie Auriault ◽  
Bernard Faugère ◽  
Alain J. Dessein
Keyword(s):  
T Cells ◽  
T Cell ◽  
Visceral Leishmaniasis ◽  
Large Fraction ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
T Cell Clones ◽  
Asymptomatic Patients ◽  
Cell Clones ◽  
Ifn Γ

ABSTRACT Visceral leishmaniasis is a severe and lethal disease caused by the protozoan parasites of the genus Leishmania. In areas where leishmaniasis is endemic, most infected individuals control the infection and remain asymptomatic; chemotherapy of visceral leishmaniasis restores some immunity which protects against relapses. In the present study, Leishmania-specific T-cell clones were established from six asymptomatic and five cured patients. Cytokines production by these clones was analyzed. A large fraction of the parasite-specific T-cell clones from asymptomatic patients were CD8+ and produced high amounts of gamma interferon (IFN-γ). Most CD4+ T-cell clones from two asymptomatic subjects exhibited an unusual phenotype: production of high levels of IFN-γ low levels of interleukin-4, (IL-4), but high levels of IL-5. In contrast, only few parasite-specific CD8+ T-cell clones were obtained from cured patients after chemotherapy; moreover, CD4+ T-cell clones from these patients exhibited an heterogeneous profile of cytokines from Th1-like to Th2-like phenotypes. These results point to CD8+ T cells and to IL-5- and IFN-γ-producing CD4+ T cells as possible contributors to human resistance to Leishmania infection. They should stimulate new immunological approaches in the control of this disease.

scholarly journals Macrophage colony-stimulating factor (CSF-1) gene expression in human T- lymphocyte clones

Blood ◽  
1991 ◽  
Vol 77 (4) ◽  
pp. 780-786 ◽  
Author(s):  
MM Hallet ◽  
V Praloran ◽  
H Vie ◽  
MA Peyrat ◽  
G Wong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Phenotypic Diversity ◽  
Calcium Ionophore ◽  
Colony Stimulating Factor ◽  
T Cell Clones ◽  
Cell Clones ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Macrophage colony stimulating factor (CSF-1) is one of several cytokines that control the differentiation, survival, and proliferation of monocytes and macrophages. A set of 11 human T-cell clones, chosen for their phenotypic diversity, were tested for their ability to express CSF-1 mRNA. After 5 hours of stimulation with phorbol myristate acetate (PMA) + calcium ionophore (Cal), all T-cell clones expressed a major 4-kb transcript, a less abundant 2-kb transcript, and several other minor species. This pattern of expression is typical for CSF-1 mRNAs. Furthermore, of the two alloreactive T-cell clones analyzed, only one showed a definitive message for CSF-1 on specific antigenic stimulation, but with delayed kinetics and less efficiency. Both conditions of stimulation induced the release of CSF-1 protein by T cells in the culture medium. Together, these findings demonstrate for the first time that normal T cells are able to produce CSF-1, previous reports being limited to two cases of tumoral cells of the T-cell lineage.

Selective Depletion of Alloreactive T Cells and Study of Anti-Tumor Activity of Specific T Cell Clones in Patients with Leukemia and Renal Carcinoma

2007 ◽  
Vol 123 ◽  
pp. S106-S107
Author(s):  
Eva Matejkova ◽  
Zuzana Hrotekova ◽  
Drahomira Kyjovska ◽  
Jaroslav Michalek ◽  
Petra Vidlakova
Keyword(s):  
T Cells ◽  
T Cell ◽  
Renal Carcinoma ◽  
T Cell Clones ◽  
Alloreactive T Cells ◽  
Cell Clones ◽  
Selective Depletion ◽  
Anti Tumor Activity

scholarly journals Evaluation of Various Strategies to Generate NPM1mut-Specific T Cell Clones

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5718-5718 ◽  
Author(s):  
Elke Ruecker-Braun ◽  
Falk Heidenreich ◽  
Cornelia S Link ◽  
Maria Schmiedgen ◽  
Rebekka Wehner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Checkpoint Inhibitors ◽  
Single Cells ◽  
Molecular Genetic ◽  
Specific Antigen ◽  
Positive Control ◽  
Low Frequencies ◽  
T Cell Clones ◽  
Cell Clones

Abstract Mutated nucleophosmin (NPM1) was identified as a promising leukemia-specific antigen for cytotoxic T lymphocytes (CTL). NPM1 is a multifunctional nucleocytoplasmic shuttling phosphoprotein. In AML patients with normal cytogenetics NPM1 mutations are the most frequent molecular genetic abnormalities, accounting for up to 60% of the patients. The peptide (AIQDLCLAV) derived from the mutated NPM1 (NPM1mut) has been described to elicit a CTL response restricted to HLA-A*02:01. We observed that NPM1mut multimer+ T cells were very rare in peripheral blood. The limitation of the multimer technology is the absence of a positive control; nevertheless it is an attractive tool to generate antigen positive T cell clones. The goal was to compare strategies for the generation of NPM1mut multimer+ T cell clones systematically. For this purpose we analyzed blood samples from two patients with AML after transplantation and six different healthy donors. We explored different strategies to isolate HLA-A*02:01 restricted NPM1mut multimer+ T single cells. The first strategy was to isolate multimer+ T cells directly from the blood without any supplements by single cell sorting. The second strategy was to sort multimer+ T cells which were previously CD8+ enriched supplementing the media either with or without IL-21. Published by Yongqing et al.IL-21 enhances the generation of human antigen-specific CD8+ T cells. A further strategy was to previously enrich CD14+ cells for the generation of autologous monocyte-derived dendritic cells (MoDCs). The co-cultivation of MoDCs loaded with the NPM1mut peptide and CD8+ cells were performed either with or without IL-21, as well. We expanded the last strategy by a second round of NPM1mut-specific stimulation. So far it was not possible to generate NPM1mut-specific T cell clones based on the advanced strategies and consistently there is no data published on NPM1mut multimer+ T cell clones. This fact raises the question why NPM1mut specific clones display such low frequencies. We want to point out that although we varied the strategies and we used eight different donors the isolation of NPM1mut-specific T cells restricted to HLA-A*02:01 apparently is challenging. Greater efforts, e.g. a larger number of donors or the use of immunological checkpoint inhibitors during cell culture are needed. Disclosures Thiede: AgenDix: Employment, Other: Ownership. Schetelig:Sanofi: Honoraria.

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