Differentiation of cytomegalovirus-specific CD8+ T cells in healthy and immunosuppressed virus carriers

Gamadia, Laila E.; Rentenaar, Rob J.; Baars, Paul A.; Remmerswaal, Ester B. M.; Surachno, S.; Weel, Jan; Toebes, Mireille; Schumacher, Ton N.; Berge, R.J.M. ten; Lier, R. A. W. Van

doi:10.1182/blood.v98.3.754

Cited by 185 publications

(187 citation statements)

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“…In contrast to NKG2C that was expressed by CCR7 -CD45RA + T cells that emerge only late in the immune response [19], NKG2A could be found at all differentiation stages occurring after the encounter with antigen. In fact, naive CD8 + T cells expressed NKG2A as early as 4-5 divisions after stimulation with IL-15 or IL-12.…”

Section: Discussionmentioning

confidence: 79%

“…By contrast, we do not believe that in humans, CD94:NKG2A expression is associated with a particular differentiation stage during an immune response. First, CMV and EBV-specific cells remain CD94 -during acute and latent infection [18][19][20]. Secondly, NKG2A -memory T cells are refractory to NKG2A induction by IL-15 or IL-12.…”

Section: Discussionmentioning

confidence: 99%

“…In humans, the situation may be quite different. The only CD94 + T cells with a known antigen specificity described to date recognize tumor-associated tissue differentiation antigens [6,[14][15][16][17], whereas CD8 + T cells specific for herpes B [18], CMV [19], or for EBV during acute mononucleosis [18,20] do not express CD94. Interestingly, many intraepithelial T lymphocytes express CD94:NKG2A [9], suggesting that its expression is induced after recognition of particular antigens and/or under particular conditions of antigenic stimulation.…”

Section: Introductionmentioning

confidence: 99%

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Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8⁺ TCR αβ lymphocytes

et al. 2004

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A subset of CD8 + T cells express the natural killer cell receptors CD94:NKG2A or CD94:NKG2C. We found that although many CD8 + T cells transcribe CD94 and NKG2C, expression of a functional CD94:NKG2C receptor is restricted to highly differentiated effector cells. CD94:NKG2A is expressed by a different subset consisting of CCR7 + memory cells and CCR7 -effector cells. Since NKG2A can only be induced on naive CD8 + T cells while CD94 -memory cells are refractory, it is likely that commitment to the CD94:NKG2A + subset occurs during the first encounter with antigen. CCR7 + CD94:NKG2A + T cells recirculate through lymph nodes where upon activation, they produce large quantities of IFN-c. These cells occur as a separate CD94:NKG2A + T cell lineage with a distinct TCR repertoire that differs from that of the other CD8 + CD94 -T cells activated in situ.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8⁺ TCR αβ lymphocytes

et al. 2004

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“…In patients with CLL, there is an expansion of a subset of CD8 + cytotoxic T cells with a CD45RA + CD27 − phenotype that is often found in immunocompromised or cytomegalovirus (CMV)-seropositive individuals [16,25] and thought to be involved in regulating CMV infection [3,35]. Thus, in patients with CLL who are undergoing lymphocyte-depleting treatment regimens, the loss of CD8 + cytotoxic T cells may provide a basis for the frequent episodes of CMV reactivation.…”

Section: Patient Predisposition To Infectionsmentioning

confidence: 99%

Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

et al. 2008

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International audienceInfection is a significant cause of morbidity and death in patients with chronic lymphocytic leukemia (CLL). Increased infectious events may arise from the multiple courses of immunosuppressive therapy and progressive deterioration of a patient's immune system over the course of disease. The humanized, anti-CD52 monoclonal antibody alemtuzumab (Campath or Campath-1H) has shown notable activity for both untreated and fludarabine-refractory CLL. The antibody not only targets malignant cells but also affects normal, healthy immune cells. The cumulative effects of the malignancy and successive courses of treatments adversely impinge on a patient's defense response to certain bacterial, fungal, and viral infections. In this review article, we provide an overview of common infectious events associated with alemtuzumab therapy in CLL. We also discuss recommendations for effectively monitoring and managing infections in CLL patients

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“…In the chronic phase of persistent infections, differences in T cell differentiation were found dependent on viral specificity [8]. In general, specific CD8 + T cell responses against CMV and other chronic viral infections found in peripheral blood (PB) were CCR7 -belonging to T EM and T EFF [8][9][10][11]. It is unclear yet, whether the failure to detect CMV-specific CCR7 + T CM is related to the specific situation of chronic infection, where continuous stimulation of T cells occurs, or is due to their retention in lymphoid tissues.…”

Section: Introductionmentioning

confidence: 99%

CMV‐specific central memory T cells reside in bone marrow

Letsch

Knödler

et al. 2007

Eur J Immunol

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CMV-specific CD8 + T cell responses in peripheral blood (PB) are characterized by a preponderance of effector and effector memory T cells. CMV-specific central memory T cells (T CM ), which are considered crucial in maintaining long-term immunity, are rarely detectable in PB. In this study we have analyzed differentiation and function of CMV pp65-specific CD8 + T cells in paired samples of human PB and BM using intracellular cytokine and tetramer staining. Overall frequencies of CMV pp65-specific T cells were similar in PB compared to BM; however, CMV-specific CD45RA -CCR7 + T CM were almost exclusively detectable in BM, which was not related to a general accumulation of T CM in BM. In vitro, CMV-specific T cells could be more efficiently expanded from BM (median 128-fold, n=6) than from PB (median 72-fold, p=0.01). Taken together, these data show that the BM is a compartment harboring CMV-specific T CM and underline the concept of the BM as a secondary immune organ. CMV specific BM-derived T CM might be a valuable source for generating T cells for adoptive transfer. IntroductionBased on phenotypic and functional characteristics two main populations of memory T cells can be distinguished: central memory T cells (T CM ), expressing the chemokine receptor CCR7, and effector memory T cells (T EM ), lacking lymph node homing receptors and migrating to peripheral tissues [1]. Both subsets can differentiate into effector T cells (T Eff ). The generally accepted concept holds that T CM have a higher proliferative potential and a greater capacity than T EM for long-lasting persistence in vivo [2][3][4].There is growing evidence suggesting that CD8 + T CM play a key role in long-term protection against acute infections in vivo [5][6][7]. In the chronic phase of persistent infections, differences in T cell differentiation were found dependent on viral specificity [8]. In general, specific CD8 + T cell responses against CMV and other chronic viral infections found in peripheral blood (PB) were CCR7 -belonging to T EM and T EFF [8][9][10][11]. It is unclear yet, whether the failure to detect CMV-specific CCR7 + T CM is related to the specific situation of chronic infection, where continuous stimulation of T cells occurs, or is due to their retention in lymphoid tissues. Information concerning the anatomical distribution of T cell differentiation subsets of virusspecific T cells in humans is very limited. In the study by Ellefsen et al.[10], however, several fold lower * These two authors contributed equally to this work. frequencies of CMV pp65-specific tetramer + CD8 + T cells were found in lymph nodes compared to PB. Recently the BM was identified as an important site for accumulation and proliferation of memory T cells [12][13][14]. Furthermore, there is growing evidence of the BM as secondary lymphoid organ priming naive T cells (T N ) and also efficiently stimulating memory T cells [15,16].In this study we comparatively analyzed the differentiation subsets of CMV pp65-specific CD8 + T cells in human PB and BM samples o...

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Differentiation of cytomegalovirus-specific CD8+ T cells in healthy and immunosuppressed virus carriers

Cited by 185 publications

References 46 publications

Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8⁺ TCR αβ lymphocytes

Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8⁺ TCR αβ lymphocytes

Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

CMV‐specific central memory T cells reside in bone marrow

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Differentiation of cytomegalovirus-specific CD8+ T cells in healthy and immunosuppressed virus carriers

Cited by 185 publications

References 46 publications

Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8+ TCR αβ lymphocytes

Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8+ TCR αβ lymphocytes

Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

CMV‐specific central memory T cells reside in bone marrow

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Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8⁺ TCR αβ lymphocytes

Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8⁺ TCR αβ lymphocytes