scholarly journals ATL-like overgrowth and clonal expansion of HTLV-1 infected CD25+ CD4+ T- lymphocyte in humanized-NOG mouse model

Retrovirology ◽  
2011 ◽  
Vol 8 (S1) ◽  
Author(s):  
Jun-ichi Fujisawa ◽  
Kenta Tezuka ◽  
Runze Xun ◽  
Mami Tei ◽  
Norihiro Takenouchi ◽  
...  
Keyword(s):  
Mouse Model ◽  
T Lymphocyte ◽  
Clonal Expansion

scholarly journals O10: METFORMIN TREATMENT IMPROVES LYMPHOCYTE METABOLISM IN A MOUSE MODEL OF MAJOR SURGERY

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
TF Jones ◽  
A Gutierrez ◽  
del Arroyo ◽  
SM Henson ◽  
GL Ackland
Keyword(s):  
T Lymphocytes ◽  
Mouse Model ◽  
T Lymphocyte ◽  
Major Surgery ◽  
P Value ◽  
Free Access ◽  
Mitochondrial Bioenergetics ◽  
Metformin Treatment ◽  
Respiratory Capacity

Abstract Introduction Lymphopaenia is common after major surgery and associated with poor outcome. T-lymphocytes restrain damaging innate inflammation. Major surgery impairs T-lymphocyte metabolism in humans, which promotes lymphopaenia. Metformin is known to improve mitochondrial bioenergetics in models of inflammation. Firstly, we hypothesised that a mouse model of major surgery would demonstrate impaired T-lymphocyte metabolism and secondly, that metformin treatment in vivo would reverse the phenotype. Method Male C57Bl/6 mice aged between 8 and 12 weeks were housed in a specific pathogen free environment with free access to food and water. Animals were dosed with either vehicle (phosphate buffered saline, 20 ml/kg) or metformin (250 mg/kg) daily via intraperitoneal injection for four days prior to and after surgery. A partial hepatectomy was performed under isofluorane anaesthesia. Naive littermates were used as controls. All experiments were performed according to the Animals (Scientific Procedures) Act 1986. Splenic T-lymphocytes were isolated by negative selection using magnetic beads. Mitochondrial bioenergetics were measured using a Seahorse Extracellular Flux analyser. Parametric statistical analysis was performed and a p-value < 0.05 was chosen to represent significance. Result T-lymphocytes demonstrated reduced spare respiratory capacity (SRC, 285 vs 497 %, p=0.004) after surgery compared to naive controls. Metformin treatment in vivo reversed this observation and SRC was comparable to naive (437 vs 497 %, p=0.34). Metformin treatment in vitro increased spare respiratory capacity in T-lymphocytes from mice after surgery compared to naive (change from untreated, 187 vs 91 %, p=0.03). Conclusion Perioperative metformin treatment improved T-lymphocyte metabolism in a mouse model of major surgery. Take-home message Metformin is a potential treatment for the lymphocyte metabolic dysfunction observed after surgery.

scholarly journals T Lymphocyte Development and Activation in Humanized Mouse Model

2019 ◽  
Vol 23 (2) ◽  
pp. 79-92 ◽  
Author(s):  
Ji Yoon Lee ◽  
A-Reum Han ◽  
Dong Ryul Lee
Keyword(s):  
Mouse Model ◽  
T Lymphocyte ◽  
Lymphocyte Development ◽  
Humanized Mouse ◽  
Humanized Mouse Model

T‐lymphocyte–specific knockout of IKK‐2 or NEMO induces T h 17 cells in an experimental nephrotoxic nephritis mouse model

2018 ◽  
Vol 33 (2) ◽  
pp. 2359-2371 ◽  
Author(s):  
Linlin Guo ◽  
Jiabin Huang ◽  
Meilan Chen ◽  
Eveline Piotrowski ◽  
Ning Song ◽  
...  
Keyword(s):  
Mouse Model ◽  
T Lymphocyte ◽  
Nephrotoxic Nephritis

scholarly journals Induction of Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Restricts Clonal Expansion of Helper T Cells

2001 ◽  
Vol 194 (7) ◽  
pp. 893-902 ◽  
Author(s):  
Alden M. Doyle ◽  
Alan C. Mullen ◽  
Alejandro V. Villarino ◽  
Anne S. Hutchins ◽  
Frances A. High ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Clonal Expansion ◽  
Negative Regulator ◽  
Lymphocyte Antigen ◽  
Cell Divisions

Cytotoxic T lymphocyte antigen (CTLA)-4 plays an essential role in immunologic homeostasis. How this negative regulator of T cell activation executes its functions has remained controversial. We now provide evidence that CTLA-4 mediates a cell-intrinsic counterbalance to restrict the clonal expansion of proliferating CD4+ T cells. The regulation of CTLA-4 expression and function ensures that, after ∼3 cell divisions of expansion, most progeny will succumb to either proliferative arrest or death over the ensuing three cell divisions. The quantitative precision of the counterbalance hinges on the graded, time-independent induction of CTLA-4 expression during the first three cell divisions. In contrast to the limits imposed on unpolarized cells, T helper type 1 (Th1) and Th2 effector progeny may be rescued from proliferative arrest by interleukin (IL)-12 and IL-4 signaling, respectively, allowing appropriately stimulated progeny to proceed to the stage of tissue homing. These results suggest that the cell-autonomous regulation of CTLA-4 induction may be a central checkpoint of clonal expansion of CD4+ T cells, allowing temporally and spatially restricted growth of progeny to be dictated by the nature of the threat posed to the host.

High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects

2007 ◽  
Vol 103 (1) ◽  
pp. 396-401 ◽  
Author(s):  
Richard J. Simpson ◽  
Geraint D. Florida-James ◽  
Cormac Cosgrove ◽  
Greg P. Whyte ◽  
Scott Macrae ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
High Intensity ◽  
Clonal Expansion ◽  
High Intensity Exercise ◽  
Antigenic Stimulation ◽  
Blood Compartment ◽  
Senescent Phenotype

Clonal expansion of T lymphocytes in response to antigenic stimulation is a fundamental process of adaptive immunity. As a consequence of clonal expansion, some T lymphocytes acquire a senescent phenotype, fail to replicate in response to further antigenic stimulation, and express the killer cell lectin-like receptor G1 (KLRG1) and/or CD57. Physical exercise elicits a mobilization of large numbers of T lymphocytes into the bloodstream from peripheral lymphoid compartments, but the frequency of senescent cells in the mobilized population is not known. Eight male runners (age: 29 ± 9 yr; maximal O2 uptake 62 ± 6 ml·kg−1·min−1) performed an intensive treadmill-running protocol at 80% maximal O2 uptake to volitional exhaustion. Blood lymphocytes isolated before, immediately after, and 1 h after exercise were assessed for cell surface expression of KLRG1, CD57, CD28, CD45RA, CD45RO, CD62L, and lymphocyte subset markers (CD3, CD4, CD8, CD56) by flow cytometry. The percentage of all CD3+ T lymphocytes expressing KLRG1 and CD57 increased with exercise ( P < 0.01). The change in T-lymphocyte KLRG1 expression was attributed to both CD4+ and CD8 bright T cells, with the relative change being greater for the CD8 bright population ( P < 0.01). Mobilized T-lymphocyte populations expressing KLRG1 and CD57 appeared to extravasate the peripheral blood compartment after 1 h of recovery. In conclusion, T lymphocytes with a senescent phenotype are mobilized and subsequently removed from the bloodstream in response to acute high-intensity exercise. This suggests that T lymphocytes contained within the peripheral lymphoid compartments that are mobilized by exercise are likely to be at a more advanced stage of biological aging and have a reduced capacity for clonal expansion than blood-resident T cells.

scholarly journals Dissection of the proliferative and differentiative signals controlling murine cytotoxic T lymphocyte responses.

1982 ◽  
Vol 155 (6) ◽  
pp. 1876-1881 ◽  
Author(s):  
H Wagner ◽  
C Hardt ◽  
B T Rouse ◽  
M Röllinghoff ◽  
P Scheurich ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
Clonal Expansion ◽  
T Cell Differentiation ◽  
Cytotoxic T Cell ◽  
Con A ◽  
Dependent Cell ◽  
Cell Differentiation Factor ◽  
Lymphocyte Responses

Evidence is presented that interleukin 2 (IL-2) is not sufficient to cause the differentiation of primary cytotoxic T lymphocytes (CTL). Sources of IL-2 were compared for their ability to cause proliferation as well as differentiation into CTL. Whereas all factors caused proliferation, only the crude Con A supernatant had cytotoxic T cell differentiation factor (CTDF) activity. Furthermore, factors absorbed with an IL-2-dependent cell line to remove IL-2 still retained CTDF activity. Thus, IL-2 functions to cause clonal expansion of CTL precursors preactivated by antigen or mitogen, but for their differentiation into CTL, an additional factor is required, here called CTDF.

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