Frequencies of Memory T Cells Specific for Varicella‐Zoster Virus, Herpes Simplex Virus, and Cytomegalovirus by Intracellular Detection of Cytokine Expression

Asanuma, Hideomi; Sharp, Margaret; Maecker, Holden T.; Maino, Vernon C.; Arvin, Ann M.

doi:10.1086/315347

Cited by 182 publications

(142 citation statements)

References 34 publications

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“…Prior to treatment, VZVspecific T cell response was mainly detected in the CD4 ϩ T cell subpopulation as only one patient had a CD8 ϩ T cell response. A similarly low frequency of VZV-specific CD8 reactivity has been observed in healthy adults, 29 indicating that VZV-induced CD4 ϩ memory T cell response is prevalent and more persistent than the CD8 memory response.…”

Section: Discussionmentioning

confidence: 74%

“…In healthy adults a similarly high level has been explained by a requirement of a more active immune surveillance to restrict replication of persistent CMV in cells of the monocyte/macrophage lineage. 29 After transplantation CMV-specific T cell recovered within months to the same or an even higher level without any of the patients having clinical symptoms or signs compatible with CMV disease. A similar association has been observed after bone marrow transplantation.…”

Section: Discussionmentioning

confidence: 95%

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Impact of high-dose chemotherapy on antigen-specific T cell immunity in breast cancer patients. Application of new flow cytometric method

Svane

Nikolajsen

Hansen

et al. 2002

Bone Marrow Transplant

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Summary:The present study analyses the influence of high-dose chemotherapy (HD) and autologous stem cell transplantation on natural and vaccine-induced specific immunity in breast cancer patients. Peripheral blood was collected from five breast cancer patients at serial time points in connection with treatment and in a follow-up period of 1 year. The frequencies of CD8 ؉ and CD4 ؉ T cells responsive to cytomegalovirus (CMV), varicella zoster virus (VZV), and tetanus in antigen-activated whole blood were determined by flow cytometric analysis of CD69, TNF␣, IFN␥ and IL-4 expression. Mononuclear cells were labelled with PKH26 dye and the CMV, VZV, and tetanus toxoid-specific proliferation of T cell subpopulations was analysed by flow cytometry. In none of the patients did the treatment result in loss of overall T cell reactivity for any of the antigens. Prior to chemotherapy 5/5 patients possessed TNF␣ expressing T cells specific for CMV, 4/5 for VZV, and 3/5 for tetanus. One year after stem cell transplantation all patients possessed TNF␣ expressing T cells specific for CMV, VZV and tetanus. The highest percentages of cytokineresponding T cells were seen after stimulation with CMV antigen. In general, the lowest reactivity (close to zero) was measured in G-CSF-mobilised blood at the time of leukapheresis. In spite of a continuously reduced CD4 to CD8 ratio after transplantation, recovery of CD4 ؉ T cells usually occurred prior to CD8 ؉ recovery and often to a higher level. The study demonstrates that natural as well as vaccine-induced specific immunity established prior to HD can be regained after stem cell transplantation. These data indicate that introduction of a preventive cancer vaccination in combination with intensive chemotherapy may be a realistic treatment option. High-dose chemotherapy (HD) has been used as an adjuvant treatment for breast cancer patients with a high risk of disease recurrence. The dose-intensive regimen profoundly impairs the immune function, especially cell mediated functions, as indicated by several reports describing both qualitative and quantitative T cell imbalances, as well as defects in the proliferative response of T cells to common activators. [1][2][3][4][5][6][7] The aim of this study was to determine the influence of HD and autologous peripheral blood stem cell transplantation (PBSCT) on natural and vaccine-induced memory T cell immunity. For this purpose a prospective study of breast cancer patients treated with HD was carried out. Qualitative and quantitative evaluation of the cellular immune system were performed in connection with treatment and in a follow-up period of 1 year. The frequencies of cytomegalovirus (CMV), varicella zoster virus (VZV) and tetanus-responsive CD8 ϩ and CD4 ϩ subpopulations of T lymphocytes were analysed in antigen (Ag)-activated whole blood and determined by flow cytometric analysis. [8][9][10][11][12][13] Analyses of the specific immune reactivity of cancer patients undergoing treatment with HD impart knowledge about the impact of intensive ...

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 95%

Impact of high-dose chemotherapy on antigen-specific T cell immunity in breast cancer patients. Application of new flow cytometric method

Svane

Nikolajsen

Hansen

et al. 2002

Bone Marrow Transplant

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“…The mean frequency of whole-HSV Agspecific memory CD4 T lymphocytes is reported to be ∼0.2% of total circulating CD4 T lymphocytes (78). Less than 5% of NK cells (probably mostly the CD56 bright CD16 2 subset) were involved in ISs, also correlating with the proportion of NK cells expressing HLA-DR (data not shown).…”

Section: Discussionmentioning

confidence: 93%

Herpes Simplex Virus Antigens Directly Activate NK Cells via TLR2, Thus Facilitating Their Presentation to CD4 T Lymphocytes

Kim

Osborne

Zeng

et al. 2012

The Journal of Immunology

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NK cells infiltrate human herpetic lesions, but their role has been underexplored. HSV can stimulate innate immune responses via surface TLR2, which is expressed on monocyte-derived dendritic cells (DCs) and NK cells. In this study, UV-inactivated HSV1/2 and immunodominant HSV2 glycoprotein D peptides conjugated to the TLR2 agonist dipalmitoyl-S-glyceryl cysteine stimulated CD4 T lymphocyte IFN-γ responses within PBMCs or in coculture with monocyte-derived DCs. NK cells contributed markedly to the PBMC responses. Furthermore, NK cells alone were activated directly by both Ags, also upregulating HLA-DR and HLA-DQ and then they activated autologous CD4 T lymphocytes. Using Transwells, Ag-stimulated NK cells and CD4 T lymphocytes were shown to interact through both cell-to-cell contact and cytokines, differing in relative importance in different donors. A distinct immunological synapse between Ag-stimulated NK cells and CD4 T lymphocytes was observed, indicating the significance of their cell-to-cell contact. A large proportion (57%) of NK cells was also in contact with CD4 T lymphocytes in the dermal infiltrate of human recurrent herpetic lesions. Thus, NK cells stimulated by TLR2-activating HSV Ags can present Ag alone or augment the role of DCs in vitro and perhaps in herpetic lesions or draining lymph nodes. In addition to DCs, NK cells should be considered as targets for adjuvants during HSV vaccine development.

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“…In addition, frequencies of VZV‐specific memory T cells are reportedly low and amount to only half of HSV‐ and to less than a tenth of CMV‐specific T‐cell frequencies in immune adults (Asanuma et al., 2000; Tyler, 2015). Together, this may add to a disrupted defense against VZV reactivation from latency.…”

Section: Discussionmentioning

confidence: 99%

Gender differences in safety issues during Fingolimod therapy: Evidence from a real‐life Relapsing Multiple Sclerosis cohort

et al. 2017

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ObjectiveBenefits and risks of new therapies in Multiple Sclerosis (MS) must be balanced carefully and tailored to patients. We aimed to describe our experience with Fingolimod (FTY), correlating demographics, clinical and hematological features of the Relapsing MS (RMS) cohort with the occurring Adverse Events (AEs).Material and MethodsPretreatment screening tests, cardiological observation, and safety follow‐up data were analyzed in 225 RMS patients. Changes in continuous data were analyzed post hoc with Wilcoxon ranks test; categorical variables were examined using McNemar test. Two‐way repeated‐measures analysis of variance (ANOVA) was used to analyze differences between baseline characteristic of the cohorts and Liver Function Tests (LFT) alterations. Binary logistic regression models were used to identify which of the baseline factors influenced LFT alterations and the occurrence of infections.ResultsDuring 2 years of follow‐up 24 patients (10%) interrupted FTY. Discontinuation most often was due to AEs (n = 14) or breakthrough disease (n = 5). The most frequently AEs were infections (10.6%). After the first year patients showing an infectious episode were mostly female (p = .04). The infections did not correlate with the decrease in white blood cells or to lymphocyte count. AST and ALT alterations were observed mostly in males (p = .002 and p = .01, respectively), and increase in GGT was reported in subjects older at FTY beginning (p < .05).ConclusionsFor a patient‐centered safety monitoring of FTY, we may apply gender‐specific warnings, for the detection of transaminases abnormalities and infectious episodes.

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Frequencies of Memory T Cells Specific for Varicella‐Zoster Virus, Herpes Simplex Virus, and Cytomegalovirus by Intracellular Detection of Cytokine Expression

Cited by 182 publications

References 34 publications

Impact of high-dose chemotherapy on antigen-specific T cell immunity in breast cancer patients. Application of new flow cytometric method

Impact of high-dose chemotherapy on antigen-specific T cell immunity in breast cancer patients. Application of new flow cytometric method

Herpes Simplex Virus Antigens Directly Activate NK Cells via TLR2, Thus Facilitating Their Presentation to CD4 T Lymphocytes

Gender differences in safety issues during Fingolimod therapy: Evidence from a real‐life Relapsing Multiple Sclerosis cohort

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