Peripheral blood lymphocytes of nonleukemic lymphoma patients exhibit aberrant expression of T-cell activation markers after polyclonal stimulation in vitro

Cancer ◽  
1990 ◽  
Vol 66 (4) ◽  
pp. 677-683 ◽  
Author(s):  
Harald Mangge ◽  
Friedrich Beaufort ◽  
Manfred Neubauer ◽  
Michael Samitz ◽  
Konrad Schauenstein
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Peripheral Blood Lymphocytes ◽  
Activation Markers ◽  
Aberrant Expression ◽  
Blood Lymphocytes

scholarly journals Direct inhibition of CDK9 blocks HIV-1 replication without preventing T-cell activation in primary human peripheral blood lymphocytes

Gene ◽  
2007 ◽  
Vol 405 (1-2) ◽  
pp. 65-78 ◽  
Author(s):  
Dominic Salerno ◽  
Muneer G. Hasham ◽  
Renée Marshall ◽  
Judit Garriga ◽  
Alexander Y. Tsygankov ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Direct Inhibition ◽  
Blood Lymphocytes ◽  
Human Peripheral Blood Lymphocytes ◽  
Hiv 1

scholarly journals CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway

Blood ◽  
2009 ◽  
Vol 114 (3) ◽  
pp. 580-588 ◽  
Author(s):  
Kathrin Gollmer ◽  
François Asperti-Boursin ◽  
Yoshihiko Tanaka ◽  
Klaus Okkenhaug ◽  
Bart Vanhaesebroeck ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Early Time ◽  
Cell Receptor ◽  
Tcr Signaling ◽  
Activation Markers

Abstract CD4+ T cells use the chemokine receptor CCR7 to home to and migrate within lymphoid tissue, where T-cell activation takes place. Using primary T-cell receptor (TCR)–transgenic (tg) CD4+ T cells, we explored the effect of CCR7 ligands, in particular CCL21, on T-cell activation. We found that the presence of CCL21 during early time points strongly increased in vitro T-cell proliferation after TCR stimulation, correlating with increased expression of early activation markers. CCL21 costimulation resulted in increased Ras- and Rac-GTP formation and enhanced phosphorylation of Akt, MEK, and ERK but not p38 or JNK. Kinase-dead PI3KδD910A/D910A or PI3Kγ-deficient TCR-tg CD4+ T cells showed similar responsiveness to CCL21 costimulation as control CD4+ T cells. Conversely, deficiency in the Rac guanine exchange factor DOCK2 significantly impaired CCL21-mediated costimulation in TCR-tg CD4+ T cells, concomitant with impaired Rac- but not Ras-GTP formation. Using lymph node slices for live monitoring of T-cell behavior and activation, we found that G protein-coupled receptor signaling was required for early CD69 expression but not for Ca2+ signaling. Our data suggest that the presence of CCL21 during early TCR signaling lowers the activation threshold through Ras- and Rac-dependent pathways leading to increased ERK phosphorylation.

scholarly journals TRPM2 Is Not Required for T-Cell Activation and Differentiation

2022 ◽  
Vol 12 ◽  
Author(s):  
Niels C. Lory ◽  
Mikolaj Nawrocki ◽  
Martina Corazza ◽  
Joanna Schmid ◽  
Valéa Schumacher ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Transient Receptor Potential ◽  
Cell Function ◽  
Intestinal Inflammation ◽  
Activation Markers

Antigen recognition by the T-cell receptor induces a cytosolic Ca2+ signal that is crucial for T-cell function. The Ca2+ channel TRPM2 (transient receptor potential cation channel subfamily M member 2) has been shown to facilitate influx of extracellular Ca2+ through the plasma membrane of T cells. Therefore, it was suggested that TRPM2 is involved in T-cell activation and differentiation. However, these results are largely derived from in vitro studies using T-cell lines and non-physiologic means of TRPM2 activation. Thus, the relevance of TRPM2-mediated Ca2+ signaling in T cells remains unclear. Here, we use TRPM2-deficient mice to investigate the function of TRPM2 in T-cell activation and differentiation. In response to TCR stimulation in vitro, Trpm2-/- and WT CD4+ and CD8+ T cells similarly upregulated the early activation markers NUR77, IRF4, and CD69. We also observed regular proliferation of Trpm2-/- CD8+ T cells and unimpaired differentiation of CD4+ T cells into Th1, Th17, and Treg cells under specific polarizing conditions. In vivo, Trpm2-/- and WT CD8+ T cells showed equal specific responses to Listeria monocytogenes after infection of WT and Trpm2-/- mice and after transfer of WT and Trpm2-/- CD8+ T cells into infected recipients. CD4+ T-cell responses were investigated in the model of anti-CD3 mAb-induced intestinal inflammation, which allows analysis of Th1, Th17, Treg, and Tr1-cell differentiation. Here again, we detected similar responses of WT and Trpm2-/- CD4+ T cells. In conclusion, our results argue against a major function of TRPM2 in T-cell activation and differentiation.

scholarly journals Expansion of a lymphocyte population co-expressing T4 (CD4) and T8 (CD8) antigens in the peripheral blood of a normal adult male

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 2024-2029 ◽  
Author(s):  
NE Kay ◽  
N Bone ◽  
M Hupke ◽  
AP Dalmasso
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Adult Male ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Normal Adult ◽  
Cd8 Cells ◽  
Blood Lymphocytes

Approximately 2% to 3% of circulating human T cells co-express CD4 and CD8 (CD4+, CD8+) T-cell antigens. These CD4+, CD8+ cells may be immature precursors that function to replenish functional T-cell subsets. We detected a very high level of CD4+, CD8+ cells in the peripheral blood lymphocytes of a healthy white male, ranging from 21% to 36%. The morphology of his peripheral blood lymphocytes was normal, and he has maintained an elevated level of CD4+, CD8+ cells without clinical disease over a 19-month observation period. The CD4+, CD8+ cells did not possess thymocyte membrane antigen (CD6), nor did they have increased Tac (CD25) antigen. His intact, purified blood T cells had a normal proliferative response to phytohemagglutinin and interleukin-2 (IL-2), provided help for B-cell proliferation at control levels and exposure to IL-2 resulted in generation of cytotoxic cells. However, the purified blood CD4+, CD8+ cells were deficient in these latter functions except for help in B-cell function. Despite defective function, the isolated CD4+, CD8+ cells co-expressed CD2 and CD3. Prolonged in vitro culture of CD4+, CD8+ cells was possible in the presence of recombinant IL-2. The cultured CD4+, CD8+ cells retained the double antigens (CD4 and CD8) throughout a 4-week period. It is likely these cells are less mature than CD4+, CD8- or CD4-, CD8+ T cells as the CD4+, CD8+ have less in vitro function than the former cells, but it is not yet clear if they mature into either CD4+, CD8-, or CD4-, CD8+ cells. Finally, the presence of an expanded, hypofunctioning CD4+, CD8+ cell population in a normal adult male is apparently compatible with excellent clinical health.

scholarly journals Imuninė stebėsena širdies transplantacijoje: atmetimo reakcijos poveikis T limfocitų žymenų ekspresijai

2010 ◽  
Vol 8 (3) ◽  
pp. 0-0
Author(s):  
Radvilė Malickaitė ◽  
Laimutė Jurgauskienė ◽  
Stanislava Simanavičienė ◽  
Vytė Valerija Maneikienė ◽  
Rita Sudikienė ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Cell Subset ◽  
Surface Glycoprotein ◽  
Ca 125 ◽  
Cell Reactivity ◽  
Activation Markers ◽  
Color Flow

Radvilė Malickaitė, Laimutė Jurgauskienė, Stanislava Simanavičienė, Vytė Valerija Maneikienė, Rita Sudikienė, Kęstutis Ručinskas Vilniaus universiteto Širdies ir kraujagyslių ligų klinikos Širdies chirurgijos centras, Santariškių g. 2, LT-08661 Vilnius El. paštas: [email protected] Darbo tikslas: Nustatyti Vilniaus universiteto ligoninės Santariškių klinikų Širdies chirurgijos centre atliekamos širdies transplantacijos įtaką T limfocitų aktyvumo rodikliams, įvertinti imuninės stebėsenos tinkamumą ūminiam transplantato atmetimui prognozuoti. Ligoniai ir metodai: Retrospektyviai analizuotas dvidešimt vieno širdies recipiento imuninių rodiklių kitimas esant normaliai potransplantacinei būklei ir ūminiam transplantato atmetimui. Periferinio kraujo imunokompetentinių ląstelių CD3+CD103+, CD4+CD103+, CD8+CD103+, CD3+CD134+, CD4+CD134+, CD8+CD134+, CD8+CD57+ ir CD8+CD38+ procentas nustatytas tėkmės citometrijos būdu. Ūminis transplantato atmetimas vertintas pagal histologinius endomiokardinės biopsijos radinius. Rezultatai: Esant ūminio atmetimo epizodams, kai endomiokardo biopsijos įvertintos ≥ 2R (3A) laipsniu, reikšmingai didėja integrino CD103 (p < 0,0001), kostimuliacinio receptoriaus CD134 (p = 0,005), antigeno CD57 (p = 0,005) ir ląstelių paviršiaus glikoproteino CD38 (p = 0,015) ekspresija citotoksinių CD8+ limfocitų paviršiuje. Išvados: Imuninė periferinio kraujo limfocitų būklės stebėsena gali būti taikoma po transplantacijos skiriamam imunosupresiniam gydymui įvertinti numatant didelę ūminio atmetimo tikimybę. Reikšminiai žodžiai: kiaušidžių cistos, supiktybėjimo rizika, piktybiškumo rizikos indeksas, ultragarsinis tyrimas, Ca-125 antigenas, chirurginis gydymas Measuring T cell reactivity for predicting heart transplant rejection Radvilė Malickaitė, Laimutė Jurgauskienė, Stanislava Simanavičienė, Vytė Valerija Maneikienė, Rita Sudikienė, Kęstutis Ručinskas Vilnius University, Clinic of Cardiovascular Diseases, Centre of Heart sSurgery, Santariškių str. 2, LT-08661 Vilnius, Lithuania E-mail: [email protected] Objective: We aimed to analyze alterations in peripheral blood T-cell subset activation compared with endomyocardial byopsy findings. Patients and methods: The study included in total twenty-one heart recipients grafted 1997–2007 at the Vilnius Heart sSurgery cCenter. T-cell activation markers CD3+CD103+, CD4+CD103+, CD8+CD103+, CD3+CD134+, CD4+CD134+, CD8+CD134+, CD8+CD57+ ir CD8+CD38+ were detected by two-color flow cytometry. Rejection was graded according to the ISHLT (the International Society of Heart and Lung Transplantation) grading system. Results: In case of ≥ 2R (3A) rejection episodes, a significant increase in the expression of integrin CD103 (p < 0.0001), co-stimulatory receptor CD134 (p = 0.005), antigen CD57 (p = 0.005) and surface glycoprotein CD38 (p = 0.015) on CD8+ T lymphocytes has been revealed. Conclusion: Immune monitoring performed on peripheral blood can be used for the assessment of immunosuppression therapy on transplant recipients’ immune response and for determining the risk of rejection. Key words: heart transplantation, acute rejection, and immune activation

scholarly journals Expansion of a lymphocyte population co-expressing T4 (CD4) and T8 (CD8) antigens in the peripheral blood of a normal adult male

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 2024-2029 ◽  
Author(s):  
NE Kay ◽  
N Bone ◽  
M Hupke ◽  
AP Dalmasso
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Adult Male ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Normal Adult ◽  
Cd8 Cells ◽  
Blood Lymphocytes

Abstract Approximately 2% to 3% of circulating human T cells co-express CD4 and CD8 (CD4+, CD8+) T-cell antigens. These CD4+, CD8+ cells may be immature precursors that function to replenish functional T-cell subsets. We detected a very high level of CD4+, CD8+ cells in the peripheral blood lymphocytes of a healthy white male, ranging from 21% to 36%. The morphology of his peripheral blood lymphocytes was normal, and he has maintained an elevated level of CD4+, CD8+ cells without clinical disease over a 19-month observation period. The CD4+, CD8+ cells did not possess thymocyte membrane antigen (CD6), nor did they have increased Tac (CD25) antigen. His intact, purified blood T cells had a normal proliferative response to phytohemagglutinin and interleukin-2 (IL-2), provided help for B-cell proliferation at control levels and exposure to IL-2 resulted in generation of cytotoxic cells. However, the purified blood CD4+, CD8+ cells were deficient in these latter functions except for help in B-cell function. Despite defective function, the isolated CD4+, CD8+ cells co-expressed CD2 and CD3. Prolonged in vitro culture of CD4+, CD8+ cells was possible in the presence of recombinant IL-2. The cultured CD4+, CD8+ cells retained the double antigens (CD4 and CD8) throughout a 4-week period. It is likely these cells are less mature than CD4+, CD8- or CD4-, CD8+ T cells as the CD4+, CD8+ have less in vitro function than the former cells, but it is not yet clear if they mature into either CD4+, CD8-, or CD4-, CD8+ cells. Finally, the presence of an expanded, hypofunctioning CD4+, CD8+ cell population in a normal adult male is apparently compatible with excellent clinical health.

Natural Toll-like Receptor Agonists for in Situ Vaccination Lymphoma Immunotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4002-4002
Author(s):  
Paul Peng ◽  
Joshua Brody ◽  
Linda Hammerich
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Clinical Grade ◽  
Toll Like Receptor ◽  
Activation Markers ◽  
Prophylactic Vaccines

Abstract Introduction: There is an unmet need for novel and effective treatments for lymphoma, the fifth most common malignancy in the US. In situ vaccination-an immunotherapeutic maneuver involving local irradiation, intratumoral (i.t.) injections of Flt3L and Toll-like receptor (TLR) agonist-has been shown in recent clinical trials (NCT00185965, NCT00880581, NCT00226993) to induce partial and complete remissions in patients with low-grade lymphoma. The strength of anti-tumor response correlates with the potency of immunogenic dendritic cells (DCs) to efficiently uptake and present tumor antigens to T cells. While the latest clinical trial NCT01976585 employs Poly-ICLC-a synthetic TLR3 agonist-to activate DCs, we hypothesize that "natural" TLR agonists (nTLRa) contained within prophylactic vaccines (e.g. live/attenuated bacteria or viruses) could simultaneously target multiple TLRs and be repurposed as clinical-grade DC activators for the in situ vaccination maneuver. Methods: Twenty-four prophylactic vaccines from our hospital's pharmacy were screened using in vitro assays for TLR ligand activity. DC subsets CD11c+ MHC-II+, CD11c+ CD11b+, and CD11c+ CD103+ were gated for flow-cytometric readouts of: (i.) activation markers (e.g. CD40, CD80, CD86, MHC class I and II), (ii.) ability to co-stimulate T cells in the context of TCR activation, as assessed by T cell activation markers (e.g. CD69, intracellular IFNγ), and (iii.) ability of nTLRa-activated DCs to induce T cell proliferation. TLR knock-out cell lines were used for dissecting the mechanistically-distinct properties of each prophylactic vaccine. Best single and combination nTLRa candidates were evaluated with the in situ vaccination maneuver in an in vivo A20 murine lymphoma model. Results: We identify a combination of vaccines Typhim, BCG-TICE, and MMR that demonstrates the ability to induce high expression of costimulatory molecules on DCs (Figure A) in vitro, as well as possessing the ability to co-stimulate in vitro T cell activation and proliferation. DC costimulation of T cell activation and proliferation is highly dependent on the "live" status of several vaccines, including BCG, MMR, Zostavax, which suggests the involvement of other pattern-recognition receptors in addition to TLRs. Cohorts of mice implanted with A20 lymphoma tumors that received i.t. injections of Typhim, BCG, MMR demonstrated slower A20 growth status post in situ vaccination maneuver, as compared to the control cohort receiving only Flt3L and irradiation (XRT). Conclusion: Prophylactic vaccines contain natural ligands to TLRs and are immediately translatable as sources of clinical-grade stimulators of dendritic cells. Combinations of the best nTLRa candidates display synergistic activation of DCs and demonstrate in vivo anti-A20 murine lymphoma immunity. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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