Age‐dependent accumulation of monoclonal CD4<sup>+</sup>CD8<sup>+</sup>double positive T lymphocytes in the peripheral blood of the elderly

Ghia, Paolo; Prato, Giuseppina; Stella, Stefania; Scielzo, Cristina; Geuna, Massimo; Caligaris-Cappio, Federico

doi:10.1111/j.1365-2141.2007.06867.x

Cited by 93 publications

(87 citation statements)

References 40 publications

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“…5 Moreover, the prevalence of MBL is age-related and population-related. Rawstron et al 6 showed that the overall prevalence of CLL-like MBL among United Kingdom hospital outpatients without hematological or oncological diseases and with normal blood counts was 3.5%.…”

Section: Epidemiologymentioning

confidence: 99%

Monoclonal B-cell lymphocytosis: a brief review for general clinicians

Matos

Falcão

2011

Sao Paulo Med. J.

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Monoclonal B-cell lymphocytosis (MBL) is a recently described medical condition that displays biological similarities to the most common subtype of adult leukemia in the Western world, i.e. chronic lymphocytic leukemia (CLL). Diagnostic criteria have been published with the aim of differentiating between these two entities. The overall prevalence of MBL is at least 100 times higher than that of CLL, which indirectly suggests that MBL is not necessarily a pre-leukemic condition, although in some circumstances, CLL cases can really be preceded by MBL. In view of this high prevalence rate, general clinicians and even non-hematological specialists have a high chance of being faced with individuals with MBL in their routine clinical practice.MBL is classified as "clinical MBL", "population-screening MBL" and "atypical MBL" and the clinical management of affected individuals depends greatly on this differentiation. The present review provides a guide to diagnosing and following up MBL patients. RESUMOA linfocitose monoclonal de células B (LMB) é uma condição médica recentemente descrita que exibe similaridades biológicas com o mais comum subtipo de leucemia em adultos de países ocidentais, qual seja, a leucemia linfocítica crônica (LLC). Critérios diagnósticos foram publicados com o intuito de separar as duas entidades. A prevalência global da LMB é pelo menos 100 vezes maior do que a da LLC, o que, indiretamente, sugere que a LMB não é necessariamente uma condição pré-leucêmica, embora, em algumas circunstâncias, casos de LLC possam realmente ser precedidos pela LMB. Em virtude dessa alta taxa de prevalência, clínicos gerais e mesmo outros especialistas não hematologistas têm grande chance de deparar-se com casos de LMB em suas rotinas clínicas. A LMB é classificada como "LMB clínica", "LMB de screening populacional" e "LMB atípica", sendo que o manuseio clínico dos indivíduos afetados depende substancialmente dessa diferenciação. A presente revisão fornece um guia para o diagnóstico e acompanhamento dos pacientes com LMB.

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Section: Epidemiologymentioning

confidence: 99%

Monoclonal B-cell lymphocytosis: a brief review for general clinicians

Matos

Falcão

2011

Sao Paulo Med. J.

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“…Peripheral CD4 + CD8 + double-positive (DP) T cells were first identified 25 years ago as a mature T-cell subpopulation accounting for about 1-2% of total T cells within healthy donor PBMCs [1], with age-dependent increase [2]. Since then, DP T cells have been described as a highly heterogeneous population with at least three subsets based on the expression levels of the CD4 and the CD8 coreceptors (CD4 high CD8 low , CD4 low CD8 high , CD4 high CD8 high ) and on the nature of the CD8 dimer (αα or αβ) [3].…”

Section: Introductionmentioning

confidence: 99%

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells

et al. 2016

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We previously demonstrated an accumulation of tumor-reactive CD4 + CD8 + double positive (DP) T cells within melanoma-infiltrating lymphocytes, supporting their role in the regulation of anti-tumor immune responses. Similarly to their CD8 + counterparts, intratumor DP T cells are MHC class-I restricted but differed by a limited lytic activity against autologous melanoma cells. Based on these observations and to further characterize DP T cells, both populations were compared at the transcriptional level. Our results revealed the overexpression of the IL-9 receptor (IL-9R) by DP T cells and prompted us to investigate the impact of IL-9 on their biology. We show that IL-9 favors DP T-cell survival by protecting them from apoptosis and by promoting their proliferation. In addition, IL-9 enhances their ability to produce cytokines and increased their levels of granzyme B/perforin as well as degranulation capacity, leading to a strengthened cytotoxic activity against melanoma cells. Taken together, the IL-9R high DP T-cell population could be a new preferential target for IL-9, which could take part in their retention within the melanoma infiltrate while also favoring their anti-tumor activity. More generally, our results extend the pleiotropic effects of IL-9 to IL-9R-expressing intra-tumor T cells, which could further potentiate anti-tumor immune responses.Keywords: CD4 + CD8 + double-positive T lymphocyte r IL-9R r IL-9 r Melanoma r TIL Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Nadine Gervois e-mail: nadine.gervois@inserm.fr IntroductionPeripheral CD4 + CD8 + double-positive (DP) T cells were first identified 25 years ago as a mature T-cell subpopulation accounting for about 1-2% of total T cells within healthy donor PBMCs Eur. J. Immunol. 2016Immunol. . 46: 1770Immunol. -1782 Tumor immunology 1771 with age-dependent increase [2]. Since then, DP T cells have been described as a highly heterogeneous population with at least three subsets based on the expression levels of the CD4 and the CD8 coreceptors (CD4 high CD8 low , CD4 low CD8 high , CD4 high CD8 high ) and on the nature of the CD8 dimer (αα or αβ) [3]. Regarding DP T cells lineage origin, two main hypotheses are still in debate. Some studies argued they step from a premature release of DP T cells from the thymus into the periphery, where their maturation into functionally competent single-positive (SP) cells continues [4,5].Others studies hypothesized that they could derive from peripheral single positive T cells. As such, IL-4 represents an important mediator of CD8αα induction on human SP CD4 T cells [6]. On the other hand, when activated in vitro via TCR cross-linking, SP CD8αβ T cells may become capable of expressing low levels of CD4 [7,8].Of interest, numerous studies reported the presence of DP T cells with, in most cases, an increased frequency in the blood and/or in the target organ of several pathological conditions (for review see [9]), such as autoimmune ...

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“…Conceivably, the progression of population-screening MBL into CLL is uncommon, 16 and most might simply be an epiphenomenon of immunosenescence, that is, an intensification of the progressive restriction of Ig and TCR repertoire observed in the elderly. [17][18][19][20] It becomes therefore important to investigate which molecular and biologic features of low-count population-screening MBL are associated with the risk of progression to focus medical attention onto the rare risky subjects and to refrain from useless and prolonged monitoring most of the otherwise healthy persons.…”

Section: Introductionmentioning

confidence: 99%

General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL

Fazi

Scarfò

Pecciarini

et al. 2011

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Age‐dependent accumulation of monoclonal CD4⁺CD8⁺double positive T lymphocytes in the peripheral blood of the elderly

Cited by 93 publications

References 40 publications

Monoclonal B-cell lymphocytosis: a brief review for general clinicians

Monoclonal B-cell lymphocytosis: a brief review for general clinicians

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells

General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL

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Age‐dependent accumulation of monoclonal CD4+CD8+double positive T lymphocytes in the peripheral blood of the elderly

Cited by 93 publications

References 40 publications

Monoclonal B-cell lymphocytosis: a brief review for general clinicians

Monoclonal B-cell lymphocytosis: a brief review for general clinicians

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4+CD8+ double‐positive T cells

General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL

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Age‐dependent accumulation of monoclonal CD4⁺CD8⁺double positive T lymphocytes in the peripheral blood of the elderly

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells