Aberrantly methylated DNA regions lead to low activation of CD4+ T-cells in IgA nephropathy

2016 ◽  
Vol 130 (9) ◽  
pp. 733-746 ◽  
Author(s):  
Fabio Sallustio ◽  
Grazia Serino ◽  
Sharon N. Cox ◽  
Alessandra Dalla Gassa ◽  
Claudia Curci ◽  
...  
Keyword(s):  
T Cells ◽  
Iga Nephropathy ◽  
Cd4 T Cells ◽  
Signal Strength ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Methylated Dna

DNA regions abnormally methylated in IgAN patients led to the reduced TCR signal strength of CD4+ T-cells and to their anomalous response, explaining the T-helper cell imbalance.

Defective T-helper cell function after T-cell–depleting therapy affecting naive and memory populations

Blood ◽  
2002 ◽  
Vol 99 (11) ◽  
pp. 4053-4062 ◽  
Author(s):  
Andreas Heitger ◽  
Patricia Winklehner ◽  
Petra Obexer ◽  
Johannes Eder ◽  
Claudia Zelle-Rieser ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Interleukin 2 ◽  
T Helper Cell ◽  
Helper Cell ◽  
High Dose ◽  
T Helper

Impaired T-cell function after T-cell– depleting (TCD) therapy has been hypothesized to be related to a transient predominance of extrathymically expanding memory T cells. To test whether after TCD therapy the naive T-helper cell population is functionally intact, the in vitro immune response of CD4+CD45RA+ (naive) and of CD4+CD45RA− (memory) cells to polyclonal mitogens (immobilized anti-CD3, phytohemagglutinin) was analyzed by flow cytometry in 22 pediatric patients after high-dose chemotherapy (including 5 after autologous and 5 after allogeneic stem cell support). At 1 to 3 months after TCD therapy, patient samples showing decreased lymphoproliferative responses also showed a reduced induction of the early activation marker CD69 by CD4+ T cells from 4 to 72 hours after stimulation even when supplemented with exogenous interleukin-2. This defect affected CD4+CD45RA− cells, but, strikingly, also CD4+CD45RA+ cells, including samples in which CD4+CD45RA+ cells were more than 90/μL, thus indicating ongoing thymopoiesis. Histogram analyses showed the median peak channel of CD69 in control CD4+CD45RA+cells rising 98-fold (median) but only 28-fold in patient cells (P < .0001). Apoptosis as detected by annexin V staining was increased in resting patient CD4+ T cells (25% versus 6%) and also affected CD4+CD45RA+ cells (12% versus 5%, P < .01). When peripheral blood mononuclear cells (PBMCs) were enriched for T cells, stimulatory responses of CD4+ cells and of CD4+CD45RA+ cells markedly improved. Thus, after TCD therapy suppressor factors contained in the non–T-cell fraction of PBMCs may affect T-helper cells irrespective of their naive or memory phenotype thus extending T-cell dysfunction to the presumably thymus-dependently regenerated T cells.

Comprehensive Intestinal T Helper Cell Profiling Reveals Specific Accumulation of IFN-γ+IL-17+Coproducing CD4+ T Cells in Active Inflammatory Bowel Disease

2014 ◽  
Vol 20 (12) ◽  
pp. 2321-2329 ◽  
Author(s):  
Anna-Maria Globig ◽  
Nadine Hennecke ◽  
Bianca Martin ◽  
Maximilian Seidl ◽  
Günther Ruf ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Bowel Disease ◽  
Cd4 T Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Specific Accumulation ◽  
Inflammatory Bowel ◽  
Ifn Γ

scholarly journals IL-12– and IL-23–induced T helper cell subsets

2005 ◽  
Vol 201 (2) ◽  
pp. 169-171 ◽  
Author(s):  
Estelle Bettelli ◽  
Vijay K. Kuchroo
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Th Cells ◽  
Th 1

Traditionally, CD4+ T cells have been separated into two different subsets named T helper (Th)1 and Th2. A new IL-23–driven subset of Th cells called ThIL-17 has now been described. The data suggest that IL-23 plays an important role in the differentiation of autoreactive pathogenic T cells. Whether these IL-23–induced ThIL-17 cells are a unique subset or are related to other Th subsets is discussed.

scholarly journals IL-17+ mast cell/T helper cell axis in the early stages of acne

2021 ◽  
Author(s):  
Yoan Eliasse ◽  
Edouard leveque ◽  
Louise Battut ◽  
Thérèse Nocera ◽  
Lucile Garidou ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Mast Cells ◽  
Cd4 T Cells ◽  
Immune Cell ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Cell Axis ◽  
Early Stages

Acne is a multifactorial disease driven by physiological changes occurring during puberty in the pilosebaceous unit (PSU) that leads to sebum overproduction and a dysbiosis involving notably Cutibacterium acnes. These changes in the PSU microenvironment lead to a shift from a homeostatic to an inflammatory state. Indeed, immunohistochemical analyses have revealed that inflammation and lymphocyte infiltration can be detected even in the infraclinical acneic stages, highlighting the importance of the early stages of the disease. In this study, we utilized a robust multi-pronged approach that included flow cytometry, confocal microscopy, and bioinformatics to comprehensively characterize the evolution of the infiltrating and resident immune cell populations in acneic lesions, beginning in the early stages of their development. Using a discovery cohort of 15 patients, we demonstrated that the composition of immune cell infiltrate is highly dynamic in nature, with the relative abundance of different cell types changing significantly as a function of clinical lesion stage. Within the stages examined, we identified a large population of CD69+ CD4+ T cells, several populations of activated antigen presenting cells, and activated mast cells producing IL-17. IL-17+ mast cells were preferentially located in CD4+ T cell rich areas and we showed that activated CD4+ T cells license mast cells to produce IL-17. Our study reveals that mast cells are the main IL-17 producers in the early stage of acne, underlying the importance of targeting the IL-17+ mast cell/T helper cell axis in therapeutic approaches.

scholarly journals Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African Population

2020 ◽  
Vol 11 ◽  
Author(s):  
Alansana Darboe ◽  
Carolyn M. Nielsen ◽  
Asia-Sophia Wolf ◽  
Jacob Wildfire ◽  
Ebrima Danso ◽  
...  
Keyword(s):  
T Cells ◽  
Life Course ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
Effector Memory ◽  
T Helper ◽  
Age Related ◽  
The Life Course

Innate lymphoid cell (ILC) lineages mirror those of CD4+ T helper cell subsets, producing type 1, 2 and 3 cytokines respectively. Studies in adult human populations have shown contributions of non-cytotoxic ILC to immune regulation or pathogenesis in a wide range of diseases and have prompted investigations of potential functional redundancy between ILC and T helper cell compartments in neonates and children. To investigate the potential for ILC to contribute to immune responses across the human lifespan, we examined the numbers and frequencies of peripheral blood ILC subsets in a cohort of Gambians aged between 5 and 73 years of age. ILC2 were the most abundant peripheral blood ILC subset in this Gambian cohort, while ILC1 were the rarest at all ages. Moreover, the frequency of ILC1s (as a proportion of all lymphocytes) was remarkably stable over the life course whereas ILC3 cell frequencies and absolute numbers declined steadily across the life course and ILC2 frequencies and absolute numbers declined from childhood until the age of approx. 30 years of age. Age-related reductions in ILC2 cell numbers appeared to be partially offset by increasing numbers of total and GATA3+ central memory (CD45RA-CCR7+) CD4+ T cells, although there was also a gradual decline in numbers of total and GATA3+ effector memory (CD45RA-CCR7-) CD4+ T cells. Despite reduced overall abundance of ILC2 cells, we observed a coincident increase in the proportion of CD117+ ILC2, indicating potential for age-related adaptation of these cells in childhood and early adulthood. While both CD117+ and CD117- ILC2 cells produced IL-13, these responses occurred predominantly within CD117- cells. Furthermore, comparison of ILC frequencies between aged-matched Gambian and UK young adults (25–29 years) revealed an overall higher proportion of ILC1 and ILC2, but not ILC3 in Gambians. Thus, these data indicate ongoing age-related changes in ILC2 cells throughout life, which retain the capacity to differentiate into potent type 2 cytokine producing cells, consistent with an ongoing role in immune modulation.

Enrichment of nucleofected primary human CD4+ T cells: A novel and efficient method for studying gene function and role in human primary T helper cell differentiation

2006 ◽  
Vol 310 (1-2) ◽  
pp. 30-39 ◽  
Author(s):  
Johanna Tahvanainen ◽  
Maritta Pykäläinen ◽  
Teemu Kallonen ◽  
Hanna Lähteenmäki ◽  
Omid Rasool ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Efficient Method ◽  
Gene Function ◽  
Cd4 T Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper

Stat5a regulates T helper cell differentiation by several distinct mechanisms

Blood ◽  
2001 ◽  
Vol 97 (8) ◽  
pp. 2358-2365 ◽  
Author(s):  
Shin-ichiro Kagami ◽  
Hiroshi Nakajima ◽  
Akira Suto ◽  
Koichi Hirose ◽  
Kotaro Suzuki ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
T Helper Cell ◽  
Interleukin 4 ◽  
Helper Cell ◽  
Wild Type ◽  
T Helper ◽  
Th2 Cell ◽  
Immunoregulatory T Cells

Abstract We have previously shown that CD4+ T cell–mediated allergic inflammation is diminished in signal transducer and activator of transcription (Stat)5a-deficient (Stat5a−/−) mice. To determine whether Stat5a regulates T helper cell differentiation, we studied T helper (Th)1 and Th2 cell differentiation of Stat5a−/−CD4+ T cells at single-cell levels. First, Th2 cell differentiation from antigen-stimulated splenocytes was significantly decreased in Stat5a−/− mice as compared with that in wild-type mice. Further, Th2 cell differentiation was also impaired in Stat5a−/− mice even when purified CD4+ T cells were stimulated with anti-CD3 plus anti-CD28 antibodies in the presence of interleukin-4. Moreover, the retrovirus-mediated gene expression of Stat5a in Stat5a−/−CD4+ T cells restored the Th2 cell differentiation at the similar levels to that in wild-type CD4+ T cells. In addition, interleukin-4 normally phosphorylated Stat6 in CD4+ T cells from Stat5a−/− mice. Second, the development of CD4+CD25+ immunoregulatory T cells was impaired in Stat5a−/− mice, as indicated by a significant decrease in the number of CD4+CD25+ T cells in Stat5a−/− mice. Furthermore, the depletion of CD4+CD25+ T cells from wild-type splenocytes significantly decreased Th2 cell differentiation but increased Th1 cell differentiation, whereas the depletion of CD4+CD25+ T cells from Stat5a−/−splenocytes had no significant effect on the Th1 and Th2 cell differentiation. Together, these results indicate that the intrinsic expression of Stat5a in CD4+ T cells is required for Th2 cell differentiation and that Stat5a is involved in the development of CD4+CD25+ immunoregulatory T cells that modulate T helper cell differentiation toward Th2 cells.

Expansion of HCV-specific T cells with a follicular T helper cell phenotype after DAA mediated antigen removal

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
M Smits ◽  
C Fauvelle ◽  
T Baumert ◽  
C Neumann-Haefelin ◽  
R Thimme ◽  
...  
Keyword(s):  
T Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
Cell Phenotype ◽  
T Helper ◽  
Antigen Removal
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