scholarly journals cDC1 Dependent Accumulation of Memory T Cells Is Required for Chronic Autoimmune Inflammation in Murine Testis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuchao Jing ◽  
Min Cao ◽  
Bei Zhang ◽  
Xuehui Long ◽  
Xiaoming Wang
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Physiological State ◽  
Phenotypic Characteristics ◽  
Autoimmune Inflammation ◽  
Comprehensive Picture ◽  
Autoimmune Orchitis ◽  
Primary Type ◽  
And Function ◽  
With Memory

As an immune privilege site, there are various types of immune cells in the testis. Previous research has been focused on the testicular macrophages, and much less is known about the T cells in the testis. Here, we found that T cells with memory phenotypes were the most abundant leukocyte in the testis except for macrophages. Our results showed that the proportion of testicular T cells increases gradually from birth to adulthood in mice and that the primary type of T cells changed from γδTCR+ T cells to αβTCR+ T cells. In addition, under homeostatic conditions, CD8+ T cells are the dominant subgroup and have different phenotypic characteristics from CD4+ T cells. We found that cDC1, but not cDC2, is necessary for the presence of T cells in the testis under physiological state. A significant decrease of T cells does not have a deleterious effect on the development of the testis or spermatogenesis. However, cDC1-dependent T cells play an indispensable role in chronic autoimmune orchitis of the testis. Collectively, our multifaceted data provide a comprehensive picture of the accumulation, localization, and function of testicular T cells.

scholarly journals Lack of Sprouty 1 and 2 enhances survival of effector CD8+ T cells and yields more protective memory cells

2018 ◽  
Vol 115 (38) ◽  
pp. E8939-E8947 ◽  
Author(s):  
Hesham M. Shehata ◽  
Shahzada Khan ◽  
Elise Chen ◽  
Patrick E. Fields ◽  
Richard A. Flavell ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Therapeutic Potential ◽  
Autoimmune Diabetes ◽  
Memory Cells ◽  
Double Knockout ◽  
And Function ◽  
I Cells ◽  
Better Than

Identifying novel pathways that promote robust function and longevity of cytotoxic T cells has promising potential for immunotherapeutic strategies to combat cancer and chronic infections. We show that sprouty 1 and 2 (Spry1/2) molecules regulate the survival and function of memory CD8+ T cells. Spry1/2 double-knockout (DKO) ovalbumin (OVA)-specific CD8+ T cells (OT-I cells) mounted more vigorous autoimmune diabetes than WT OT-I cells when transferred to mice expressing OVA in their pancreatic β-islets. To determine the consequence of Spry1/2 deletion on effector and memory CD8+ T cell development and function, we used systemic infection with lymphocytic choriomeningitis virus (LCMV) Armstrong. Spry1/2 DKO LCMV gp33-specific P14 CD8+ T cells survive contraction better than WT cells and generate significantly more polyfunctional memory T cells. The larger number of Spry1/2 DKO memory T cells displayed enhanced infiltration into infected tissue, demonstrating that absence of Spry1/2 can result in increased recall capacity. Upon adoptive transfer into naive hosts, Spry1/2 DKO memory T cells controlled Listeria monocytogenes infection better than WT cells. The enhanced formation of more functional Spry1/2 DKO memory T cells was associated with significantly reduced mTORC1 activity and glucose uptake. Reduced p-AKT, p-FoxO1/3a, and T-bet expression was also consistent with enhanced survival and memory accrual. Collectively, loss of Spry1/2 enhances the survival of effector CD8+ T cells and results in the formation of more protective memory cells. Deleting Spry1/2 in antigen-specific CD8+ T cells may have therapeutic potential for enhancing the survival and functionality of effector and memory CD8+ T cells in vivo.

scholarly journals Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1

2017 ◽  
Vol 215 (1) ◽  
pp. 51-62 ◽  
Author(s):  
Mark Y. Jeng ◽  
Philip A. Hull ◽  
Mingjian Fei ◽  
Hye-Sook Kwon ◽  
Chia-Lin Tsou ◽  
...  
Keyword(s):  
T Cells ◽  
Molecular Mechanisms ◽  
Memory T Cells ◽  
Cell Metabolism ◽  
Global Gene Expression ◽  
Metabolic Reprogramming ◽  
Transcriptional Reprogramming ◽  
Age Related ◽  
Global Gene Expression Profiling ◽  
And Function

The expansion of CD8+CD28– T cells, a population of terminally differentiated memory T cells, is one of the most consistent immunological changes in humans during aging. CD8+CD28– T cells are highly cytotoxic, and their frequency is linked to many age-related diseases. As they do not accumulate in mice, many of the molecular mechanisms regulating their fate and function remain unclear. In this paper, we find that human CD8+CD28– T cells, under resting conditions, have an enhanced capacity to use glycolysis, a function linked to decreased expression of the NAD+-dependent protein deacetylase SIRT1. Global gene expression profiling identified the transcription factor FoxO1 as a SIRT1 target involved in transcriptional reprogramming of CD8+CD28– T cells. FoxO1 is proteasomally degraded in SIRT1-deficient CD8+CD28– T cells, and inhibiting its activity in resting CD8+CD28+ T cells enhanced glycolytic capacity and granzyme B production as in CD8+CD28– T cells. These data identify the evolutionarily conserved SIRT1–FoxO1 axis as a regulator of resting CD8+ memory T cell metabolism and activity in humans.

Phenotype and function of circulating memory T cells in human vitiligo*

2020 ◽  
Vol 183 (5) ◽  
pp. 899-908 ◽  
Author(s):  
C. Martins ◽  
A.‐S. Darrigade ◽  
C. Jacquemin ◽  
T. Barnetche ◽  
A. Taieb ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
And Function

scholarly journals CD8α+Dendritic CellTransPresentation of IL-15 to Naive CD8+T Cells Produces Antigen-Inexperienced T Cells in the Periphery with Memory Phenotype and Function

2013 ◽  
Vol 190 (5) ◽  
pp. 1936-1947 ◽  
Author(s):  
Tomasz Sosinowski ◽  
Jason T. White ◽  
Eric W. Cross ◽  
Catherine Haluszczak ◽  
Philippa Marrack ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory Phenotype ◽  
And Function ◽  
With Memory

scholarly journals CD137 stimulation delivers an antigen-independent growth signal for T lymphocytes with memory phenotype

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4882-4889 ◽  
Author(s):  
Yuwen Zhu ◽  
Gefeng Zhu ◽  
Liqun Luo ◽  
Andrew S. Flies ◽  
Lieping Chen
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Memory Phenotype ◽  
Costimulatory Receptor ◽  
Functional Maturation ◽  
Receptor Signal ◽  
Vigorous Growth ◽  
With Memory

Abstract CD137 has long been recognized as a costimulatory receptor for growth and functional maturation of recently activated T cells in the presence of T-cell receptor signal. In this report, we present the fact that, in the absence of MHC and antigen, triggering of CD137 by an agonist monoclonal antibody induces vigorous growth of both CD8+ and CD4+ T cells with memory phenotype, whereas it does not affect naive T cells. Moreover, T cells with memory phenotype accumulate progressively in transgenic mice overexpressing CD137 ligand. CD137-mediated proliferation of memory T cells is directly through CD137 on T cells and does not require IL-15 and IFN-γ. Our results define a new role of CD137 signal in the growth of memory T cells.

scholarly journals Dynamic T cell migration program provides resident memory within intestinal epithelium

2010 ◽  
Vol 207 (3) ◽  
pp. 553-564 ◽  
Author(s):  
David Masopust ◽  
Daniel Choo ◽  
Vaiva Vezys ◽  
E. John Wherry ◽  
Jaikumar Duraiswamy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Intestinal Mucosa ◽  
Memory T Cells ◽  
Yellow Fever Vaccine ◽  
Cell Mediated Immunity ◽  
T Cell Migration ◽  
Local Cell ◽  
Alternative Routes ◽  
With Memory

Migration to intestinal mucosa putatively depends on local activation because gastrointestinal lymphoid tissue induces expression of intestinal homing molecules, whereas skin-draining lymph nodes do not. This paradigm is difficult to reconcile with reports of intestinal T cell responses after alternative routes of immunization. We reconcile this discrepancy by demonstrating that activation within spleen results in intermediate induction of homing potential to the intestinal mucosa. We further demonstrate that memory T cells within small intestine epithelium do not routinely recirculate with memory T cells in other tissues, and we provide evidence that homing is similarly dynamic in humans after subcutaneous live yellow fever vaccine immunization. These data explain why systemic immunization routes induce local cell-mediated immunity within the intestine and indicate that this tissue must be seeded with memory T cell precursors shortly after activation.

scholarly journals Alloreactive and leukemia-reactive T cells are preferentially derived from naive precursors in healthy donors: implications for immunotherapy with memory T cells

Haematologica ◽  
2011 ◽  
Vol 96 (7) ◽  
pp. 1024-1032 ◽  
Author(s):  
E. Distler ◽  
A. Bloetz ◽  
J. Albrecht ◽  
S. Asdufan ◽  
A. Hohberger ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Healthy Donors ◽  
With Memory

scholarly journals In Vivo Blockade of Murine ARTC2.2 During Cell Preparation Preserves the Vitality and Function of Liver Tissue-Resident Memory T Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Björn Rissiek ◽  
Marco Lukowiak ◽  
Friederike Raczkowski ◽  
Tim Magnus ◽  
Hans-Willi Mittrücker ◽  
...  
Keyword(s):  
T Cells ◽  
Liver Tissue ◽  
Memory T Cells ◽  
Cell Preparation ◽  
And Function ◽  
Resident Memory T Cells

scholarly journals Immune Dysregulation after Cardiothoracic Surgery and Incidental Thymectomy: Maintenance of Regulatory T Cells despite Impaired Thymopoiesis

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Nancy J. Halnon ◽  
Paige Cooper ◽  
Diana Yu Hui Chen ◽  
M. Ines Boechat ◽  
Christel H. Uittenbogaart
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Congenital Heart ◽  
Memory T Cells ◽  
Immune Dysregulation ◽  
Cardiothoracic Surgery ◽  
Immune Disorders ◽  
Treg Number ◽  
And Function ◽  
Dsdna Antibodies

Thymectomy is performed in infants during cardiothoracic surgery leaving many patients with reduced thympopoiesis. An association between immune disorders and regulatory T cells (Treg) after incidental thymectomy has not been investigated. Questionnaires soliciting symptoms of atopic or autoimmune disease and biomarkers were measured in children and adults with congenital heart disease and either reduced or preserved thymopoiesis. Tregs were examined. Atopic or autoimmune-like symptoms and elevated anti-dsDNA antibodies were common after surgery in individuals with low thymopoiesis. Total Treg number and function were maintained but with fewer naïve Treg. TCR spectratypes were similar to other memory T cells. These data suggest that thymectomy does not reduce total Treg number but homeostasis is affected with reduced naïve Treg. Prevalence of autoimmune or atopic symptoms after surgery is not associated with total number or proportion of Tregs but appears to be due to otherwise unknown factors that may include altered Treg homeostasis.

Sign in / Sign up

Export Citation Format

Share Document