scholarly journals Renal ischemia-reperfusion leads to long term infiltration of activated and effector-memory T lymphocytes

2009 ◽  
Vol 75 (5) ◽  
pp. 526-535 ◽  
Author(s):  
Miguel Ascon ◽  
Dolores B. Ascon ◽  
Manchang Liu ◽  
Chris Cheadle ◽  
Chaitali Sarkar ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Effector Memory ◽  
Memory T Lymphocytes

Abstract P332: Role of T-Lymphocytes in the Long-Term Blood Pressure and Renal Disease Effects of Acute Renal Ischemia-Reperfusion Injury

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Bernardo Lopez ◽  
Galina Petrova ◽  
Justine M Abais-Battad ◽  
Hayley Lund ◽  
Daniel Fehrenbach ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Renal Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Immunosuppressive Agents ◽  
High Salt ◽  
Renal Ischemia ◽  
Salt Sensitive Hypertension

Epidemiological data indicates that acute kidney injury (AKI) is an independent risk factor for the development of hypertension and chronic kidney disease in patients. Previous studies demonstrated that rats develop sodium-dependent hypertension and kidney damage following experimental AKI induced by a renal ischemia-reperfusion (IR) insult; furthermore, these high salt deleterious effects could be blunted by administration of immunosuppressive agents. The present study was performed on Dahl SS (SS) rats and SS rats with a null mutation in the CD247 gene (SS-CD247) leading to depletion of T-lymphocytes in order to specifically examine the role of T cells in this response (n=5-6 rats/group). As assessed by serum creatinine (SCr) levels, no difference was observed in the initial response to IR injury between SS and SS-CD247: SCr increased from 0.44±0.03 to 2.16±0.32 mg/dl in SS rats 24 hours after an initial 30 minute period of renal ischemia and returned to control levels after 8 days of recovery. Moreover, no differences were noted in mean arterial pressure (MAP) or albumin excretion rate (UAlb) between SS and SS-CD247 after 43 days of recovery from IR injury while the rats were maintained on a low salt (0.4% NaCl) diet. When the rats were fed a 4.0% NaCl diet for two weeks, MAP and UAlb significantly increased in the sham SS to 178±9 mmHg and 189±25 mg/day, respectively; values significantly greater than observed in the sham SS-CD247 rats (148±2 mmHg and 87±17 mg/day). As expected, the SS rats recovered from IR injury demonstrated an exaggerated increase in MAP (peaking at 183±2 mmHg) and UAlb (275±54 mg/day) in response to high salt. There was no difference in the number of total CD3+ lymphocytes in the kidneys of IR and sham SS after high salt, though the ratio of CD4+/CD8+ T cells was increased in the IR group. Compared to sham CD247, an exaggerated elevation of MAP (157±9 mmHg) and UAlb (210±32 mg/day) was also observed in the SS-CD247 rats recovered from IR injury, demonstrating enhanced responsiveness following IR injury in animals lacking T cells. These data indicate that T lymphocytes amplify salt-sensitive hypertension and renal damage, but other mechanisms also mediate the salt-sensitive hypertension and renal damage that occurs in animals recovered from IR injury.

scholarly journals Antigen-independent accumulation of activated effector/memory T lymphocytes into human and murine tumors

2005 ◽  
Vol 118 (5) ◽  
pp. 1205-1214 ◽  
Author(s):  
Nathalie T. Joncker ◽  
Marie-Annick Marloie ◽  
Anna Chernysheva ◽  
Christophe Lonchay ◽  
Simone Cuff ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Effector Memory ◽  
Murine Tumors ◽  
Memory T Lymphocytes

The Humanized Anti PD-1 Antibody, CT-011, Increases Specific CD4+ Effector/Memory and Memory T Lymphocytes in Patients with Diffuse Large B Cell Lymphoma (DLBCL) Following Autologous Stem Cell Transplantation (AuSCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1216-1216
Author(s):  
Rinat Rotem-Yehudar ◽  
Philippe Armand ◽  
Steve Devine ◽  
Joseph W. Fay ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
B Cell Lymphoma ◽  
Peripheral Tolerance ◽  
Effector Memory ◽  
Memory Cells ◽  
Antibody Treatment ◽  
Effector Memory Cells ◽  
Memory T Lymphocytes ◽  
Memory Lymphocytes

Abstract Abstract 1216 Poster Board I-238 Background: PD-1 (Program Death-1), an immune inhibitory receptor and its ligands PD-L1 and PD-L2, participate in peripheral tolerance and play a key role in immune suppression and evasion mechanisms in cancer and chronic infectious diseases. PD-1 inhibits activation signals and functions as a pro-apoptotic receptor in effector lymphocytes, and consequently regulates the extent and duration of specific adaptive and innate immune responses. CT-011, a humanized antibody, blocks the function of PD-1, resulting in increased activities of T and NK cells in vitro and in enhanced tumor immunity in experimental tumor models. At the molecular level, the antibody enhances PI3K-mediated survival and trafficking signals, attenuates cell death in effector/memory (CD4+CD45RO+) cells, and enhances trafficking in response to Stromal Cell-derived Factor-1 (SDF-1). We hypothesized that CT-011 would enhance effector/memory cells in patients with DLBCL after AuSCT and delay recurrence. Methods: We treated 41 patients (pts) with DLBCL from 30-90 days after AuSCT with CT-011 and now report data on effector/memory and memory lymphocytes in the first 30 pts. CT-011 was given at a dose of 1.5mg/kg for 3 doses, 6 weeks apart. The primary endpoint was to determine the proportion of patients who have not relapsed or died within 18 months following autologous PBSCT, and it is too early for that analysis. Our secondary endpoint was to measure the number of effector /memory and memory lymphocytes before and after treatment, and those data are the subject of this report. Results: Flow cytometry analyses (Table) on pre (baseline: BL) and post-treatment blood samples from the first 30 pts enrolled show elevated levels of specific effector/memory and memory CD4+ T lymphocytes following treatment with CT-011; the median absolute number (ABS) of effector/memory CD4+CD45RO+CD62L-CCR7- cells was increased by +49% from BL (p<0.05) 6 weeks following the first treatment with CT-011, reaching a 2 fold increase in the ABS levels from BL and a 45% increase in the median percentage of the total lymphocyte population (p<0.05) 4 weeks after the third antibody treatment (week 16). The percentage of peripheral memory CD4+ CD62L-CD127+ cells was also increased by 61% from BL (median, p<0.05) on week 16. The observed increase, particularly of the effector/memory CD4+CD45RO+CD62L-CCR7- lymphocytes, a subset directly linked to PD-1 activity and to tumor immune surveillance, likely indicates a specific cellular response to CT-011, since no significant changes were observed for other memory cell subsets including CD4+CD45RO+CD62L+CCR7+cells, CD4+ CD62L+CD127+ cells, CD8+ CD62L-CD127+, CD8+CD62L+CD127+ cells or CD4+CD25+ FOXP3+ suppressor T cells. Overall no changes were observed in the level of total lymphocytes or T cells throughout 16 weeks of follow up from the 1st antibody treatment. Transient reduction of 32% (median, p<0.05) and 25% (median, p<0.05) in the ABS levels of CD3+CD8+ and CD3+CD45RO+, respectively, was observed at week 12, which recovered to baseline or higher levels on week 16. These changes may be explained by trafficking or recycling of CD8+ effector/memory cells from the periphery to target organs. Conclusions: Consistent with its mechanism of action, CT-011 increases the levels of specific CD4+ effector/memory and memory T lymphocytes. This is the first demonstration of safe induction of effector memory and memory lymphocytes, essential components of tumor- immune control, in lymphoma patients following AuSCT. This antibody may have promise for the treatment of lymphoma. Disclosures: Rotem-Yehudar: Cure Tech: Employment. Gordon:Cure Tech: Membership on an entity's Board of Directors or advisory committees.

scholarly journals The Abnormal CD4+T Lymphocyte Subset Distribution and Vbeta Repertoire in New-onset Rheumatoid Arthritis Can Be Modulated by Methotrexate Treament

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 871 ◽  
Author(s):  
Jorge Monserrat ◽  
Cristina Bohórquez ◽  
Ana María Gómez Lahoz ◽  
Atusa Movasat ◽  
Ana Pérez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Lymphocytes ◽  
Effector Memory ◽  
Disease Modifying Drugs ◽  
Tcr Repertoire ◽  
Before And After ◽  
Polychromatic Flow Cytometry ◽  
Pre Treatment ◽  
Vbeta Repertoire

Patients with long-term, treated, rheumatoid arthritis (RA) show abnormalities in their circulating CD4+ T-lymphocytes, but whether this occurs in recently diagnosed naïve patients to disease-modifying drugs (DMARDs) is under discussion. These patients show heterogeneous clinical response to methotrexate (MTX) treatment. We have examined the count of circulating CD4+ T-lymphocytes, and their naïve (TN), central memory (TCM), effector memory (TEM) and effector (TE) subsets, CD28 expression and Vβ TCR repertoire distribution by polychromatic flow cytometry in a population of 68 DMARD-naïve recently diagnosed RA patients, before and after 3 and 6 months of MTX treatment. At pre-treatment baseline, patients showed an expansion of the counts of CD4+ TN, TEM, TE and TCM lymphocyte subsets, and of total CD4+CD28− cells and of the TE subset with a different pattern of numbers in MTX responder and non-responders. The expansion of CD4+TEM lymphocytes showed a predictive value of MTX non-response. MTX treatment was associated to different modifications in the counts of the CD4+ subsets and of the Vβ TCR repertoire family distribution and in the level of CD28 expression in responders and non-responders. In conclusion, the disturbance of CD4+ lymphocytes is already found in DMARD-naïve RA patients with different patterns of alterations in MTX responders and non-responders.

scholarly journals The blocking of CXCR3 and CCR5 suppresses the infiltration of T lymphocytes in rat renal ischemia reperfusion

2012 ◽  
Vol 27 (10) ◽  
pp. 3799-3806 ◽  
Author(s):  
K. Tsutahara ◽  
M. Okumi ◽  
Y. Kakuta ◽  
T. Abe ◽  
K. Yazawa ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Ischemia Reperfusion ◽  
Renal Ischemia
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