Cytomegalovirus contributes partly to uraemia-associated premature immunological ageing of the T cell compartment

Meijers, Ruud W. J.; Litjens, Nicolle H.R.; Wit, Elly A. de; Langerak, Anton W.; Spek, Ashley van der; Baan, Carla C.; Weimar, Willem; Betjes, Michiel G. H.

doi:10.1111/cei.12188

Cited by 34 publications

(49 citation statements)

References 36 publications

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“…Thus, premature immunological aging is a dominant feature in patients with end-stage renal failure (30,31). In addition, CMV has been shown to contribute to the uremiaassociated premature aging of the T cell system that is associated with high percentages of CD57 þ CD28null CD8þ effector-memory T cells, which is likely a consequence of oligoclonal expansions of CMV-specific CD8þ T cells (30,32). CD57 þ CD28null CD8þ effector-memory T cells have been reported to have a high IFNg production in healthy young and middle-aged CMV-seropositive individuals (16).…”

Section: Discussionmentioning

confidence: 99%

Factors Related to the Development of CMV-Specific CD8+ T cell Response in CMV-Seropositive Solid Organ Transplant Candidates

Cantisán

Rodelo-Haad

Páez-Vega

et al. 2015

American Journal of Transplantation

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This cross-sectional study analyzes factors associated with the development of CMV-specific CD8þ response, measured by IFNg production after cytomegalovirus (CMV) peptide stimulation, in CMV-seropositive solid organ transplantation candidates. A total of 114 candidates were enrolled, of whom 22.8% (26/114) were nonreactive (IFNg < 0.2 IU/mL). Multivariate logistic regression analysis showed that age, HLA alleles and organ to be transplanted were associated with developing CMV-specific CD8þ immunity (reactive; IFNg ! 0.2 IU/mL). The probability of being reactive was higher in candidates over 50 than in those under 50 (OR 6.33,). Candidates with HLA-A1 and/or HLA-A2 alleles had a higher probability of being reactive than those with non-HLA-A1/non-HLA-A2 alleles (OR 10.97,. Renal candidates had a higher probability of being reactive than lung (adjusted OR 8.85,) and liver candidates (OR 4.87,). The AUC of this model was 0.84 (p < 0.001). Positive and negative predictive values were 84.8% and 76.9%, respectively. In renal candidates longer dialysis was associated with an increased frequency of reactive individuals (p ¼ 0.040). Therefore, although the assessment of CMV-specific CD8þ response is recommended in all Rþ candidates, it is essential in those with a lower probability of being reactive, such as non-renal candidates, candidates under 50 or those with non-HLA-A1/non-HLA-A2 alleles.

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Section: Discussionmentioning

confidence: 99%

Factors Related to the Development of CMV-Specific CD8+ T cell Response in CMV-Seropositive Solid Organ Transplant Candidates

Cantisán

Rodelo-Haad

Páez-Vega

et al. 2015

American Journal of Transplantation

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“…MSC were isolated, cultured and characterized as described previously [19]. In brief, perirenal adipose tissue was disrupted mechanically and digested enzymatically with collagenase type IV (Life Technologies, Paisley, UK).…”

Section: Origin Isolation and Culture Of Human Mscmentioning

confidence: 99%

Mesenchymal stem cells control alloreactive CD8+CD28− T cells

Engela

Baan

Litjens

et al. 2013

Clinical and Experimental Immunology

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“…CMV seroposivity, is associated with alterations in parameters related to aging of T cells such as reduced telomere length and the induction of differentiated CD4 þ and CD8 þ T cells (1)(2)(3)(4). A characteristic feature of these differentiated T cells in CMV-seropositive individuals is the higher number of CD4 þ as well as CD8 þ T cells lacking the surface expression of CD28, a costimulatory molecule that is lost late in the course of T cell differentiation (5,6).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, the appearance of significant numbers of circulating CD4 þ CD28null T cells is related to CMV seropositivity and ESRD further promotes their expansion (7,8). CMV infection also contributes to the uremia-associated premature immunological aging of ESRD patients as it is associated with a reduced telomere length in CD8 þ T cells (3).…”

Section: Introductionmentioning

confidence: 99%

Primary Cytomegalovirus Infection Significantly Impacts Circulating T Cells in Kidney Transplant Recipients

Meijers

Litjens

Hesselink

et al. 2015

American Journal of Transplantation

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Cytomegalovirus (CMV) infection profoundly affects the T cell compartment and is associated with alterations in T cell aging parameters and generation of cytotoxic CD4þ CD28null T cells. Hence, the effect of a primary CMV infection post-kidney transplantation (KT) on the peripheral T cell compartment was examined. As aging parameters, we determined the T cell differentiation status, T cell receptor excision circle (TREC) content, CD31þ na€ ıve T cell numbers and relative telomere length (RTL) pre-KT and 12 months post-KT. CMV-seronegative KT recipients, receiving a kidney from a CMV-seropositive donor (Dþ/RÀ) were compared to Dþ/Rþ KT recipients. Eleven out of the 22 Dþ/RÀ KT recipients had CMV viremia post-KT. They developed CMV-specific CD4 þ and CD8 þ T cells and their T cell compartment shifted towards a more differentiated memory phenotype with expansion of CD4 þ CD28null and CD8 þ CD28null cells. One year post-KT, the CD8 þ T cell count was almost doubled compared to nonviremic Dþ/RÀ and Dþ/Rþ KT recipients. In addition, the RTL of the CD8 þ T cell was significantly lower and both the TREC content and CD31 þ na€ ıve T cell numbers significantly decreased. Moreover, primary CMV infection was associated with a negative impact on glomerular filtration rate. In conclusion, primary CMV infection has a substantial impact on the number and phenotype of peripheral T cells and may negatively affect renal allograft function.

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Cytomegalovirus contributes partly to uraemia-associated premature immunological ageing of the T cell compartment

Cited by 34 publications

References 36 publications

Factors Related to the Development of CMV-Specific CD8+ T cell Response in CMV-Seropositive Solid Organ Transplant Candidates

Factors Related to the Development of CMV-Specific CD8+ T cell Response in CMV-Seropositive Solid Organ Transplant Candidates

Mesenchymal stem cells control alloreactive CD8+CD28− T cells

Primary Cytomegalovirus Infection Significantly Impacts Circulating T Cells in Kidney Transplant Recipients

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