Population doublings of murine CD4+ memory T cells during continuous antigen stimulation in vivo

2014 ◽  
Vol 292 (1-2) ◽  
pp. 45-52 ◽  
Author(s):  
Yoshihiro Kushida ◽  
Jun-ya Ishida ◽  
Masato Fujii ◽  
Maki Touma ◽  
Masamichi Hosono
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Antigen Stimulation ◽  
Population Doublings

scholarly journals Peripheral T lymphocyte depletion by apoptosis after CD4 ligation in vivo: selective loss of CD44− and ‘activating’ memory T cells

2008 ◽  
Vol 95 (1) ◽  
pp. 195-200 ◽  
Author(s):  
S. E. M. HOWIE ◽  
A. J. SOMMERFIELD ◽  
E. GRAY ◽  
D. J. HARRISON
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Memory T Cells ◽  
Lymphocyte Depletion ◽  
Selective Loss

scholarly journals Chronic Antigen Stimulation In Vivo Induces a Distinct Population of Antigen-Specific Foxp3−CD25− Regulatory T Cells

2007 ◽  
Vol 179 (12) ◽  
pp. 8059-8068 ◽  
Author(s):  
Wiebke Hansen ◽  
Astrid M. Westendorf ◽  
Simone Reinwald ◽  
Dunja Bruder ◽  
Stefanie Deppenmeier ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Distinct Population ◽  
Antigen Stimulation

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 A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maria M. Klicznik ◽  
Ariane Benedetti ◽  
Laura M. Gail ◽  
Suraj R. Varkhande ◽  
Raimund Holly ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Human Skin ◽  
Memory T Cells ◽  
Humanized Mouse ◽  
Humanized Mouse Model

scholarly journals IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell–mediated rejection of systemic lymphoma in immunodeficient mice

Blood ◽  
2010 ◽  
Vol 115 (17) ◽  
pp. 3508-3519 ◽  
Author(s):  
John C. Markley ◽  
Michel Sadelain
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adoptive Transfer ◽  
Memory T Cells ◽  
Tumor Rejection ◽  
Effector Memory ◽  
Transfer Model ◽  
Human T Cell

Abstract The γc-cytokines are critical regulators of immunity and possess both overlapping and distinctive functions. However, comparative studies of their pleiotropic effects on human T cell–mediated tumor rejection are lacking. In a xenogeneic adoptive transfer model, we have compared the therapeutic potency of CD19-specific human primary T cells that constitutively express interleukin-2 (IL-2), IL-7, IL-15, or IL-21. We demonstrate that each cytokine enhanced the eradication of systemic CD19+ B-cell malignancies in nonobese diabetic/severe combined immunodeficient (NOD/SCID)/γcnull mice with markedly different efficacies and through singularly distinct mechanisms. IL-7– and IL-21–transduced T cells were most efficacious in vivo, although their effector functions were not as enhanced as IL-2– and IL-15–transduced T cells. IL-7 best sustained in vitro T-cell accumulation in response to repeated antigenic stimulation, but did not promote long-term T-cell persistence in vivo. Both IL-15 and IL-21 overexpression supported long-term T-cell persistence in treated mice, however, the memory T cells found 100 days after adoptive transfer were phenotypically dissimilar, resembling central memory and effector memory T cells, respectively. These results support the use of γc-cytokines in cancer immunotherapy, and establish that there exists more than 1 human T-cell memory phenotype associated with long-term tumor immunity.

scholarly journals Antigen challenge leads to in vivo activation and elimination of highly polarized TH1 memory T cells

2002 ◽  
Vol 99 (9) ◽  
pp. 6187-6191 ◽  
Author(s):  
N. Hayashi ◽  
D. Liu ◽  
B. Min ◽  
S. Z. Ben-Sasson ◽  
W. E. Paul
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Antigen Challenge

Anti-Thymocyte Globulin (ATG) Differentially Depletes naïve and Memory T Cells and Permits Memory-Type Regulatory T Cells

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4670-4670
Author(s):  
Chang-Qing Xia ◽  
Anna Chernatynskaya ◽  
Clive Wasserfall ◽  
Benjamin Looney ◽  
Suigui Wan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Memory T Cells ◽  
Conflicts Of Interest ◽  
T Cell Subsets ◽  
Hematopoietic Stem

Abstract Abstract 4670 Anti-thymocyte globulin (ATG) has been used in clinic for the treatment of allograft rejection and autoimmune diseases. However, its mechanism of action is not fully understood. To our knowledge, how ATG therapy affects naïve and memory T cells has not been well investigated. In this study, we have employed nonobese diabetic mouse model to investigate how administration of anti-thymocyte globulin (ATG) affects memory and naïve T cells as well as CD4+CD25+Foxp3+ regulatory T cells in peripheral blood and lymphoid organs; We also investigate how ATG therapy affects antigen-experienced T cells. Kinetic studies of peripheral blood CD4+ and CD8+ T cells post-ATG therapy shows that both populations decline to their lowest levels at day 3, while CD4+ T cells return to normal levels more rapidly than CD8+ T cells. We find that ATG therapy fails to eliminate antigen-primed T cells, which is consistent with the results that ATG therapy preferentially depletes naïve T cells relative to memory T cells. CD4+ T cell responses post-ATG therapy skew to T helper type 2 (Th2) and IL-10-producing T regulatory type 1 (Tr1) cells. Intriguingly, Foxp3+ regulatory T cells (Tregs) are less sensitive to ATG depletion and remain at higher levels following in vivo recovery compared to controls. Of note, the frequency of Foxp3+ Tregs with memory-like immunophenotype is significantly increased in ATG-treated animals, which might play an important role in controlling effector T cells post ATG therapy. In summary, ATG therapy may modulate antigen-specific immune responses through modulation of naïve and memory T cell pools and more importantly through driving T cell subsets with regulatory activities. This study provides important data for guiding ATG therapy in allogenieic hematopoietic stem cell transplantation and other immune-mediated disorders. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Homeostatic cytokines orchestrate the segregation of CD4 and CD8 memory T-cell reservoirs in mice

Blood ◽  
2011 ◽  
Vol 118 (11) ◽  
pp. 3039-3050 ◽  
Author(s):  
Lili Yang ◽  
Yang Yu ◽  
Manorama Kalwani ◽  
Tai-Wei Joy Tseng ◽  
David Baltimore
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Memory T Cells ◽  
Quantitative Distribution ◽  
Memory T Cell ◽  
Peripheral Lymph ◽  
Cytokine Stimulation ◽  
Homeostatic Cytokines

Abstract Memory T cells (TMs) have been detected in many tissues but their quantitative distribution remains largely undefined. We show that in mice there is a remarkably biased accumulation of long-term CD4 TMs into mucosal sites (mainly gut, especially Peyer patches), and CD8 TMs into lymph nodes and spleen (in particular, peripheral lymph nodes [PLNs]). This distinction correlates with their differentiated expression of PLN- and gut-homing markers. CD8 and CD4 TMs selectively require the expression of PLN-homing marker CCR7 or gut-homing marker α4β7 for maintenance. PLNs and gut supply CD8 and CD4 TMs with their individually favored homeostatic cytokine, IL-15, or IL-7. Cytokine stimulation in turn regulates the different gut-homing marker expression on CD4 and CD8 TMs. IL-15 plays a major role in vivo regulating CD8 TMs homing to PLNs. Thus, the reservoir segregation of CD4 and CD8 TMs meets their individual needs for homeostatic cytokines and is under feedback control of cytokine stimulation.

Response of naïve and memory CD8+ T cells to antigen stimulation in vivo

10.1038/76907 ◽  
2000 ◽  
Vol 1 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Henrique Veiga-Fernandes ◽  
Ulrich Walter ◽  
Christine Bourgeois ◽  
Angela McLean ◽  
Benedita Rocha
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory Cd8 T Cells ◽  
Antigen Stimulation

scholarly journals Antigen-Responsive CD4+ T Cells from C3H Mice Chronically Infected with Leishmania amazonensis Are Impaired in the Transition to an Effector Phenotype

2006 ◽  
Vol 74 (3) ◽  
pp. 1547-1554 ◽  
Author(s):  
Amanda E. Ramer ◽  
Yannick F. Vanloubbeeck ◽  
Douglas E. Jones
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
T Cell Response ◽  
Leishmania Amazonensis ◽  
Effector Memory ◽  
Intrinsic Defect ◽  
Antigen Stimulation ◽  
Ifn Γ

ABSTRACT C3HeB/FeJ mice challenged with Leishmania major develop a polarized Th1 response and subsequently heal, whereas Leishmania amazonensis challenge leads to chronic lesions with high parasite loads at 10 weeks postinfection. In this study, a comparison of draining lymph node cells from L. amazonensis- and L. major-infected mice at 10 weeks postinfection showed equivalent percentages of effector/memory phenotype CD44hi CD4+ T cells producing interleukin-2 (IL-2) and proliferating after antigen stimulation. However, these cells isolated from L. amazonensis-infected mice were not skewed toward either a Th1 or Th2 phenotype in vivo, as evidenced by their unbiased Th1/Th2 transcription factor mRNA profile. In vivo antigen stimulation with added IL-12 failed to enhance gamma interferon (IFN-γ) production of CD4+ T cells from L. amazonensis-infected mice. Antigen stimulation of CD4+ T cells from L. amazonensis-infected mice in vitro in the presence of IL-12 resulted in production of only 10 to 15% of the IFN-γ produced by T cells from L. major-infected mice under identical conditions. These results suggest that the CD4+ T-cell response during chronic L. amazonensis infection is limited during the transition from an early activated CD4+ T-cell population to an effector cell population and demonstrate that these T cells have an intrinsic defect beyond the presence or absence of IL-12 during antigen stimulation.

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