CD56+ T cells are increased in kidney transplant patients following cytomegalovirus infection

Almehmadi, Mazen; Hammad, Abdul; Heyworth, Sally; Moberly, Jane; Middleton, D.; Hopkins, Mark; Hart, Ian; Christmas, Stephen E.

doi:10.1111/tid.12405

Cited by 9 publications

(6 citation statements)

References 43 publications

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“…CMV-specific CD8 T cells also express the NKRs CD56 and CD57. CD56 + CD8 T cells are known for their natural killer-like cytotoxicity [51], and CD56 is shown on CMV-specific T cells in renal transplant patients [52] and healthy individuals (unpublished observations, S. van den Berg and D. van Baarle). CD57 expression represents a cellular phenotype associated with poor proliferative capacity but high cytotoxic potential [53].…”

Section: The Differentiation Phenotype Of Cmv-specific Cd8 T Cellsmentioning

confidence: 99%

The hallmarks of CMV-specific CD8 T-cell differentiation

Berg

Pardieck

Lanfermeijer

et al. 2019

Med Microbiol Immunol

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Upon cytomegalovirus (CMV) infection, large T-cell responses are elicited that remain high or even increase over time, a phenomenon named memory T-cell inflation. Besides, the maintained robust T-cell response, CMV-specific T cells seem to have a distinctive phenotype, characterized by an advanced differentiation state. Here, we will review this "special" differentiation status by discussing the cellular phenotype based on the expression of CD45 isoforms, costimulatory, inhibitory and natural killer receptors, adhesion and lymphocyte homing molecules, transcription factors, cytokines and cytotoxic molecules. In addition, we focus on whether the differentiation state of CMV-specific CD8 T cells is unique in comparison with other chronic viruses and we will discuss the possible impact of factors such as antigen exposure and aging on the advanced differentiation status of CMV-specific CD8 T cells.

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Section: The Differentiation Phenotype Of Cmv-specific Cd8 T Cellsmentioning

confidence: 99%

The hallmarks of CMV-specific CD8 T-cell differentiation

Berg

Pardieck

Lanfermeijer

et al. 2019

Med Microbiol Immunol

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“…Proportions of both CD56+ T cells and B cells expressing HLA-G were significantly increased following stimulation in vitro of leucocytes from healthy subjects with CMV antigens [36] and also in kidney transplant patients in vivo [44]. It remains possible that immunosuppressive drug treatment of leucocytes in vitro permitted sub-clinical emergence of latent CMV in positive subjects, leading to enhancement of HLA-G expression.…”

Section: Discussionmentioning

confidence: 99%

Changes in HLA-G Expression by Leucocyte Subsets Following Renal Transplantation and the Effect of Immunosuppressive Drugs on Leucocyte HLA-G Expression in Vitro

Al-Bayati¹,

Heyworth²,

Moberly³

et al. 2018

obm transplant

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Background: HLA-G is an immunosuppressive molecule with a potential role in allograft acceptance. Methods: Expression of HLA-G on leucocyte subpopulations was studied in a group of 21 renal transplant patients immediately prior to and 2 months post-transplantation. Results: Significant increases in proportions of total HLA-G+CD4+ T cells were seen (0.5+/-0.1% to 7.9+/-3.2%; p<0.01) and also for CD45RA+, CD45RO+ and CD69+ subsets. Increases in proportions of HLA-G+ cells were also seen in CD8+ T cells and their subsets, CD56+ T cells, B cells, NK cells and monocytes, and also of serum soluble HLA-G, but these did not reach statistical significance. When leucocytes from healthy subjects were cultured for 7 days in

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“…Indeed, increased proportions of HCMV-specific CD8 + CD56 + T cells have previously been described to be associated with primary or reactivating HCMV infections. 48,49 These CD56 + T cells are cytotoxic to HCMV infected tumor cells and express distinct KIR, DNAM-1 receptors and a transcriptional gene signature that is unique from NK cells and Vα24 + Vβ11 + invariant NKT. 50,51 An alternative explanation for the source of these cells is that they were not recruited from peripheral blood, but indeed, expanded from CD103 + resident T cells.…”

Section: Discussionmentioning

confidence: 99%

Increased infiltration and tolerised antigen-specific CD8⁺ T_EM cells in tumor but not peripheral blood have no impact on survival of HCMV⁺ glioblastoma patients

et al. 2017

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Human cytomegalovirus (HCMV) antigens in glioblastoma (GBM) present opportunities for personalised immunotherapy. However, their presence in GBM tissue is still under debate, and evidence of their impact on functional immune responses and prognosis is sparse. Here, we investigated the presence of pp65 (UL83) and immediate early 1 (IE-1) HCMV antigens in a cohort of Norwegian GBM patients (n = 177), using qPCR, immunohistochemistry, and serology. HCMV status was then used to investigate whether viral antigens influenced immune cell phenotype, infiltration, activation and patient survival. Pp65 and IE-1 were detected by qPCR in 23% and 43% of GBM patients, respectively. Furthermore, there was increased seropositivity in GBM patients relative to donors (79% vs. 48%, respectively; Logistic regression, OR = 4.05, 95%CI [1.807-9.114], P = 0.001, also when adjusted for age (OR = 2.84, 95%CI [1.110-7.275], P = 0.029). Tissue IE-1-positivity correlated with increased CD3+CD8+ T-cell infiltration (P < 0.0001), where CD8+ effector memory T (TEM) cells accounted for the majority of CD8+T cells compared with peripheral blood of HCMV+ patients (P < 0.0001), and HCMV+ (P < 0.001) and HCMV− (P < 0.001) donors. HLA-A2/B8-restricted HCMV-specific CD8+ T cells were more frequent in blood and tumor of HCMV+ GBM patients compared with seronegative patients, and donors irrespective of their serostatus. In biopsies, the HCMV-specific CD8+ TEM cells highly expressed CTLA-4 and PD-1 immune checkpoint protein markers compared with populations in peripheral blood (P < 0.001 and P < 0.0001), which expressed 3-fold greater levels of CD28 (P < 0.001 and P < 0.0001). These peripheral blood T cells correspondingly secreted higher levels of IFNγ in response to pp65 and IE-1 peptide stimulation (P < 0.001). Thus, despite apparent increased immunogenicity of HCMV compared with tumor antigens, the T cells were tolerised, and HCMV status did not impact patient survival (Log Rank3.53 HR = 0.85 95%CI [0.564-1.290], P = 0.45). Enhancing immune functionality in the tumor microenvironment thus may improve patient outcome.

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CD56+ T cells are increased in kidney transplant patients following cytomegalovirus infection

Abstract: The results show significant increases in proportions of CD56+ T cells in relation to CMV infection in renal transplant patients and suggest that these cells have a cytotoxic function against CMV-infected cells.

Cited by 9 publications

References 43 publications

The hallmarks of CMV-specific CD8 T-cell differentiation

The hallmarks of CMV-specific CD8 T-cell differentiation

Changes in HLA-G Expression by Leucocyte Subsets Following Renal Transplantation and the Effect of Immunosuppressive Drugs on Leucocyte HLA-G Expression in Vitro

Increased infiltration and tolerised antigen-specific CD8⁺ T_EM cells in tumor but not peripheral blood have no impact on survival of HCMV⁺ glioblastoma patients

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CD56+ T cells are increased in kidney transplant patients following cytomegalovirus infection

Abstract: The results show significant increases in proportions of CD56+ T cells in relation to CMV infection in renal transplant patients and suggest that these cells have a cytotoxic function against CMV-infected cells.

Cited by 9 publications

References 43 publications

The hallmarks of CMV-specific CD8 T-cell differentiation

The hallmarks of CMV-specific CD8 T-cell differentiation

Changes in HLA-G Expression by Leucocyte Subsets Following Renal Transplantation and the Effect of Immunosuppressive Drugs on Leucocyte HLA-G Expression in Vitro

Increased infiltration and tolerised antigen-specific CD8+ TEM cells in tumor but not peripheral blood have no impact on survival of HCMV+ glioblastoma patients

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Increased infiltration and tolerised antigen-specific CD8⁺ T_EM cells in tumor but not peripheral blood have no impact on survival of HCMV⁺ glioblastoma patients