Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammapathy".

Posnett, David N.; Sinha, Rakhi; Kabak, Shara; Russo, Carlo

doi:10.1084/jem.179.2.609

Cited by 737 publications

(512 citation statements)

References 37 publications

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“…In contrast, comparison between the patient groups showed a higher frequency of CD8ϩ,CD28-null T cells in patients with extraarticular RA than in those with limited RA (P Ͻ 0.05). Consistent with previous reports (24), younger healthy persons (ages 19-34 years) had a significantly lower frequency of CD8ϩ,CD28-null T cells than older healthy persons ages Ն39 years (P Յ 0.008). The latter finding also indicates an influence of age on CD28 loss in CD8ϩ T cells.…”

Section: Resultssupporting

confidence: 91%

“…In contrast, there is an even higher level of in vivo accumulation of CD56ϩ T cells among RA patients, which is disproportionate with age. Similar age-related in vivo accumulation of CD28-null T cells has been reported (23,24), whereas RA patients have even higher frequencies irrespective of age (8,9) (Figure 2A). These findings support the idea of accelerated senescence in 54 MICHEL ET AL RA (17), with CD28-null,CD56ϩ T cells being prototypic senescent or presenescent lymphocytes.…”

Section: Discussionsupporting

confidence: 83%

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CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

Michel

Turesson

Lemster

et al. 2007

Arthritis & Rheumatism

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Objective. T cells deficient in CD28 expression have been implicated in the pathogenesis of rheumatoid arthritis (RA). Given that CD28-null T cells are functionally heterogeneous, we undertook this study to screen for novel receptors on these cells.Methods. Seventy-two patients with RA (ages 35-84 years) and 53 healthy persons (32 young controls ages 19-34 years, 21 older controls ages 39-86 years) were recruited. Phenotypes and proliferative capacity of T cells from fresh leukocytes and of long-term cultures were monitored by flow cytometry. Lung biopsy specimens from patients with RA-associated interstitial pneumonitis (IP) were examined by immunohistochemistry. Receptor functionality was assessed by crosslinking bioassays.Results. Chronic stimulation of CD28؉ T cells in vitro yielded progenies that lacked CD28 but that gained CD56. Ex vivo analysis of leukocytes from patients with extraarticular RA showed a higher frequency of CD56؉,CD28-null T cells than in patients with disease confined to the joints or in healthy controls. CD56؉,CD28-null T cells had nil capacity for proliferation, consistent with cellular senescence. CD56؉ T cells had skewed T cell receptor (TCR) ␣/␤-chain usage and restricted TCR third complementarity-determining region spectra. Histologic studies showed that CD56؉ T cells were components of cellular infiltrates in RAassociated IP. CD56 crosslinking on T cells sufficiently induced cytokine production, although CD56/TCR coligation induced higher production levels.Conclusion. Chronic activation of T cells induces counterregulation of CD28 and CD56 expression. The loss of CD28 is accompanied by the gain of CD56 that confers TCR-independent and TCR-dependent activation pathways. We propose that accumulation of CD56؉ T cells in RA contributes to maladaptive immune responses and that CD56؉ T cells are potential targets for therapy.

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Section: Resultssupporting

confidence: 91%

Section: Discussionsupporting

confidence: 83%

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

Michel

Turesson

Lemster

et al. 2007

Arthritis & Rheumatism

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“…From the Old template, five clusters appeared to be memory CD4 T cells (CD3+CD4+CD8−CD45−), three expressed monocytic markers (CD3−CD14+CD11B+), and four expressed both T cell and monocyte markers and showed high FSC‐W values, consistent with T cell/monocyte conjugates. The T cell results fit well with previous studies that showed a shift in frequency from naïve to memory CD8 T cells on aging 18, 19, 20, 21, consistent with the accumulation of memory cells with continued antigen stimulation, and oligoclonal expansion of specific memory CD8 T cell populations 22, 23. Similarly, a decrease in gamma‐delta T cells has been reported previously 24, 25.…”

Section: Resultssupporting

confidence: 90%

Competitive SWIFT cluster templates enhance detection of aging changes

Rebhahn

Roumanes

et al. 2015

Cytometry Pt A

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Clustering‐based algorithms for automated analysis of flow cytometry datasets have achieved more efficient and objective analysis than manual processing. Clustering organizes flow cytometry data into subpopulations with substantially homogenous characteristics but does not directly address the important problem of identifying the salient differences in subpopulations between subjects and groups. Here, we address this problem by augmenting SWIFT—a mixture model based clustering algorithm reported previously. First, we show that SWIFT clustering using a “template” mixture model, in which all subpopulations are represented, identifies small differences in cell numbers per subpopulation between samples. Second, we demonstrate that resolution of inter‐sample differences is increased by “competition” wherein a joint model is formed by combining the mixture model templates obtained from different groups. In the joint model, clusters from individual groups compete for the assignment of cells, sharpening differences between samples, particularly differences representing subpopulation shifts that are masked under clustering with a single template model. The benefit of competition was demonstrated first with a semisynthetic dataset obtained by deliberately shifting a known subpopulation within an actual flow cytometry sample. Single templates correctly identified changes in the number of cells in the subpopulation, but only the competition method detected small changes in median fluorescence. In further validation studies, competition identified a larger number of significantly altered subpopulations between young and elderly subjects. This enrichment was specific, because competition between templates from consensus male and female samples did not improve the detection of age‐related differences. Several changes between the young and elderly identified by SWIFT template competition were consistent with known alterations in the elderly, and additional altered subpopulations were also identified. Alternative algorithms detected far fewer significantly altered clusters. Thus SWIFT template competition is a powerful approach to sharpen comparisons between selected groups in flow cytometry datasets. © 2015 The Authors. Published Wiley Periodicals Inc.

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“…In such circumstances, only single-cell gene rearrangement study of tumor-infiltrating T-lymphocytes in non-Hodgkin's B-cell lymphoma-affected tissues could address this issue (52). Clonal populations of nonneoplastic T-cells have also been described in patients with B-cell chronic lymphocytic leukemia and multiple myeloma (53,54) and even in healthy elderly humans (55).…”

Section: Discussionmentioning

confidence: 99%

PCR Analysis of Immunoglobulin Heavy Chain (IgH) and TcR-γ Chain Gene Rearrangements in the Diagnosis of Lymphoproliferative Disorders: Results of a Study of 525 Cases

et al. 2000

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This report summarizes a cumulative 4-year experience in polymerase chain reaction (PCR) analysis of immunoglobin heavy chain (IgH) and TcR-␥ chain gene rearrangements in 525 cases of lymphoproliferative disorders. Because the sensitivity of the PCR methodology was found to be tissue dependent, in the study of the presence of clonal cell population in tissues containing a small number of polyclonal lymphocytes, such as skin and gastrointestinal biopsy specimens, we used the multiple-PCR run approach. In this latter methodology, we repeat the PCR reaction from the same sample at least three times to confirm the reproducibility of the results. In the study of 273 cases of B-or T-cell lymphomas with characteristic immunomorphological and clinical features, a clonal IgH or TcR-␥ chain gene rearrangement was detected in approximately 80% of cases. A clonal rearrangement involving both IgH and TcR-␥ chain genes was found in 10% of cases of both B-cell and T-cell lymphomas. The study of 167 cases of nonneoplastic lymphoid tissue samples showed the presence of clonally rearranged cell populations for IgH or TcR-␥ genes in 3 and 9% of cases, respectively. We also applied PCR for the study of 85 cases of lymphoproliferations with no definite diagnosis (i.e., benign versus malignant) after immunomorphological analysis. In 65 cases (76%), the correlation of immunomorphological features with the presence (48 cases) or the absence (17 cases) of clonal lymphoid cell populations led to a definite diagnosis. In almost all these cases, the final diagnosis was found to be in agreement with the clinical course. In the 20 remaining cases (24%), no definite diagnosis could be made. We also assessed the value of PCR in detecting bcl-2/J H gene rearrangement as an additional clonal marker in the diagnosis of follicular lymphoma. Bcl-2/J H rearrangement and/or IgH gene rearrangement was found in approximately 85% (71/85) of follicular lymphoma cases studied.

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Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammapathy".

Cited by 737 publications

References 37 publications

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

Competitive SWIFT cluster templates enhance detection of aging changes

PCR Analysis of Immunoglobulin Heavy Chain (IgH) and TcR-γ Chain Gene Rearrangements in the Diagnosis of Lymphoproliferative Disorders: Results of a Study of 525 Cases

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