scholarly journals T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Emma T. M. Peereboom ◽  
Benedict M. Matern ◽  
Toshihide Tomosugi ◽  
Matthias Niemann ◽  
Julia Drylewicz ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
T Cell ◽  
T Helper Cells ◽  
Graft Failure ◽  
Surrogate Marker ◽  
Kidney Graft ◽  
T Cell Epitopes ◽  
T Helper ◽  
Risk Of Death ◽  
Helper Cells

CD4+ T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+ memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+ memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+ memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4+ memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation.

Vaccine-Induced, Pseudorabies Virus-Specific, Extrathymic CD4+CD8+ Memory T-Helper Cells in Swine

1998 ◽  
Vol 72 (6) ◽  
pp. 4866-4873 ◽  
Author(s):  
Bertram T. Ober ◽  
Artur Summerfield ◽  
Christina Mattlinger ◽  
Karl-Heinz Wiesmüller ◽  
Günther Jung ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mhc Class Ii ◽  
T Helper Cells ◽  
Pseudorabies Virus ◽  
Class Ii ◽  
T Cell Epitopes ◽  
T Helper ◽  
Helper Cells

ABSTRACT Pseudorabies virus (PRV; suid herpesvirus 1) infection causes heavy economic losses in the pig industry. Therefore, vaccination with live attenuated viruses is practiced in many countries. This vaccination was demonstrated to induce extrathymic virus-specific memory CD4+CD8+ T lymphocytes. Due to their major histocompatibility complex (MHC) class II-restricted proliferation, it is generally believed that these T lymphocytes function as memory T-helper cells. To directly prove this hypothesis, 15-amino-acid, overlapping peptides of the viral glycoprotein gC were used for screening in proliferation assays with peripheral blood mononuclear cells of vaccinated d/d haplotype inbred pigs. In these experiments, two naturally processed T-cell epitopes (T1 and T2) which are MHC class II restricted were identified. It was shown that extrathymic CD4+CD8+ T cells are the T-lymphocyte subpopulation that responds to epitope T2. In addition, we were able to show that cytokine secretion can be induced in these T cells through recall with inactivated PRV and demonstrated that activated PRV-primed CD4+CD8+ T cells are able to induce PRV-specific immunoglobulin synthesis by PRV-primed, resting B cells. Taken together, these results demonstrate that the glycoprotein gC takes part in the priming of humoral anti-PRV memory responses. The experiments identified the first T-cell epitopes so far known to induce the generation of virus-specific CD4+CD8+ memory T lymphocytes and showed that CD4+CD8+ T cells are memory T-helper cells. Therefore, this study describes the generation of virus-specific CD4+CD8+ T cells, which is observed during vaccination, as a part of the potent humoral anti-PRV memory response induced by the vaccine.

scholarly journals Neonatal lymphocyte subpopulations analysis and maternal preterm premature rupture of membranes: a pilot study

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Margherita Amadi ◽  
Silvia Visentin ◽  
Francesca Tosato ◽  
Paola Fogar ◽  
Giulia Giacomini ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
T Helper Cells ◽  
Lymphocyte Subpopulations ◽  
T Helper ◽  
Premature Rupture Of Membranes ◽  
Premature Rupture ◽  
Preterm Premature Rupture ◽  
Helper Cells

Abstract Objectives Preterm premature rupture of membranes (pPROM) causes preterm delivery, and increases maternal T-cell response against the fetus. Fetal inflammatory response prompts maturation of the newborn’s immunocompetent cells, and could be associated with unfavorable neonatal outcome. The aims were to examine the effects of pPROM (Mercer BM. Preterm premature rupture of the membranes: current approaches to evaluation and management. Obstet Gynecol Clin N Am 2005;32:411) on the newborn’s and mother’s immune system and (Test G, Levy A, Wiznitzer A, Mazor M, Holcberg G, Zlotnik A, et al. Factors affecting the latency period in patients with preterm premature rupture of membranes (pPROM). Arch Gynecol Obstet 2011;283:707–10) to assess the predictive value of immune system changes in neonatal morbidity. Methods Mother-newborn pairs (18 mothers and 23 newborns) who experienced pPROM and controls (11 mothers and 14 newborns), were enrolled. Maternal and neonatal whole blood samples underwent flow cytometry to measure lymphocyte subpopulations. Results pPROM-newborns had fewer naïve CD4 T-cells, and more memory CD4 T-cells than control newborns. The effect was the same for increasing pPROM latency times before delivery. Gestational age and birth weight influenced maturation of the newborns’ lymphocyte subpopulations and white blood cells, notably cytotoxic T-cells, regulatory T-cells, T-helper cells (absolute count), and CD4/CD8 ratio. Among morbidities, fewer naïve CD8 T-cells were found in bronchopulmonary dysplasia (BPD) (p=0.0009), and more T-helper cells in early onset sepsis (p=0.04). Conclusions pPROM prompts maturation of the newborn’s T-cell immune system secondary to antigenic stimulation, which correlates with pPROM latency. Maternal immunity to inflammatory conditions is associated with a decrease in non-major histocompatibility complex (MHC)-restricted cytotoxic cells.

Combined Immunophenotyping and Karyotyping in Peripheral T Cell Lymphomas Demonstrating Different Clonal and Nonclonal Chromosome Aberrations in T Helper Cells

1994 ◽  
Vol 15 (1-2) ◽  
pp. 113-125 ◽  
Author(s):  
B. Schlegelberger ◽  
K. Weber-Matthiesen ◽  
W. Sterry ◽  
H. Bartels ◽  
R. Sonnen ◽  
...  
Keyword(s):  
T Cell ◽  
Chromosome Aberrations ◽  
T Helper Cells ◽  
T Helper ◽  
Helper Cells ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

KS01.3.A Tumoral MHC class II expression in gliomas drives T cell exhaustion

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii3-ii3
Author(s):  
Y Chih ◽  
K Sahm ◽  
A Sadik ◽  
T Bunse ◽  
N Trautwein ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
T Helper Cells ◽  
Glioma Cell Line ◽  
Human Glioma ◽  
T Helper ◽  
Transcriptomic Data ◽  
Helper Cells ◽  
Mhcii Expression

Abstract BACKGROUND Neoepitopes are presented on major histocompatibility class II (MHCII) molecules. In glioma, for instance, the recurrent driver mutation IDH1R132H was shown to bear an MHCII-restricted epitope in preclinical and clinical vaccine studies. The general relevance of MHCII expression in glioma for antitumor immunity, however, remains unknown. Here we evaluate stromal and tumoral MHCII expression, functionality, and its association with survival in gliomas. MATERIAL AND METHODS Immunostaining of human glioma tissues was used to identify tumoral, endothelial, and microglial MHCII expression and to enumerate T cell infiltrates. To gain insights into tumoral MHCII expression, bulk transcriptomic data from TCGA and single-cell transcriptomic data from publicly available datasets were analyzed. MHC ligandome analyses of an MHCII+ glioma cell line and human glioma tissues were used to determine the functionality of MHCII in vitro and ex vivo. Functional in vitro co-culture assays with an HLA-DR-matched tetanus toxoid (TT) epitope-overexpressing glioma cell line and in vitro-expanded TT-reactive T cells from healthy donors were used to examine direct target recognition by T helper cells. CRISPR-Cas9-mediated knockout of MHCII in preclinical hypermutant glioblastoma cell line GL261 was employed to further validate the consequences of tumoral MHCII expression and to probe potential clinical intervention with existing therapies. RESULTS MHCII is expressed in the majority of gliomas and associated with increased infiltration of T cells. In 10% of the analyzed glioma tissues and a subset of single cells, tumoral MHCII expression is detected. Clinical and transcriptomic data reveal that tumoral MHCII is associated with poor prognosis, cytokine responses, immune inhibition and T cell differentiation. Ligandome analyses evidence presentation of peptides by MHCII molecules on glioma cells. In in vitro assays, TT-reactive T helper cells specifically produce IFNg when co-cultured with MHCII+ glioma cells upon the presence of co-stimulation. In agreement with the clinical data, preclinical murine models demonstrate that tumoral MHCII expression leads to reduced survival. Co-culture assay shows that tumoral MHCII results in upregulation of PD-1 on T helper cells antigen-specifically. Concordantly, immune checkpoint blockade (ICB) therapy slows the disease progression of mice carrying MHCII+ tumors. CONCLUSION MHCII is expressed in gliomas by a subset of tumor cells. Although tumoral MHCII is functional, it is associated with poor survival in both clinical data and preclinical models. T cell exhaustion induced by tumoral MHCII expression can, in part, be overcome by ICB in vivo. Further experiments are required to decipher tumor cell intrinsic and microenvironmental consequences of tumoral MHCII expression.

scholarly journals Angioimmunoblastic T cell lymphoma is derived from mature T-helper cells with varying expression and loss of detectable CD4

2002 ◽  
Vol 103 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Seung-Sook Lee ◽  
Thomas Rüdiger ◽  
Tobias Odenwald ◽  
Sabine Roth ◽  
Petr Starostik ◽  
...  
Keyword(s):  
T Cell ◽  
T Helper Cells ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
T Helper ◽  
Angioimmunoblastic T Cell Lymphoma ◽  
Helper Cells
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