TOTAL AND "ACTIVATED" PERIPHERAL BLOOD T LYMPHOCYTES IN PATIENTS WITH THYROID DISORDERS

1977 ◽  
Vol 85 (4) ◽  
pp. 753-759 ◽  
Author(s):  
J. R. Wall ◽  
B. Gray ◽  
D. M. Greenwood
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Recovery Phase ◽  
Subacute Thyroiditis ◽  
Graves Disease ◽  
Thyroid Disorders ◽  
Activated T Cells ◽  
Activated T Lymphocytes ◽  
Low Levels

ABSTRACT The percentage of total and "activated" peripheral blood T lymphocytes was measured in patients with (i) hyperthyroid Graves' disease selected for absence of ophthalmopathy, (ii) treated Graves' disease, with ophthalmopathy, and (iii) other thyroid disorders including subacute thyroiditis, using sheep red blood cell rosette tests. No patient had significantly increased levels of either total or "activated" T lymphocytes. On the other hand, the percentage of total T cells was below normal in 8 of 18 patients with hyperthyroid Graves' disease and in 6 of 18 patients with ophthalmopathy compared with only one of 12 patients with nodular goitres. Similarly, low levels of "activated" T cells were demonstrated in 5 of 18 patients with hyperthyroid Graves' disease and in 10 of 18 patients with ophthalmopathy compared with only one of 12 patients with nodular goitres. Three of four patients with subacute thyroiditis tested had depressed levels of total T lymphocytes whilst only one had low levels of "activated" T lymphocytes. Levels returned to normal during the recovery phase in the two patients with positive tests who were retested. Depressed levels of T lymphocyte populations in patients with Graves' disease and subacute thyroiditis may be due to feedback suppression and/or "exhaustion" in association with the thyroidal and orbital immunological reactions.

scholarly journals BINDING OF AGGREGATED γ-GLOBULIN TO ACTIVATED T LYMPHOCYTES IN THE GUINEA PIG

1974 ◽  
Vol 139 (4) ◽  
pp. 1002-1012 ◽  
Author(s):  
John A. van Boxel ◽  
David L. Rosenstreich
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Lymphocytes ◽  
Guinea Pig ◽  
Surface Membrane ◽  
Cell Populations ◽  
Cell Marker ◽  
Activated T Cells ◽  
Activated T Lymphocytes

Heat-aggregated guinea pig γ-globulin was shown to bind to the surface membrane of a subclass of guinea pig T lymphocytes. Cells of this subpopulation were identified as T lymphocytes because these cells did not stain for surface Ig (a B-cell marker) but did form spontaneous E-rosettes with rabbit erythrocytes (a T-cell marker). A strikingly high proportion of such aggregate-binding (Agg+), E-rosette-forming (E-rosette+), but surface Ig-negative (Ig-) cells were found in an inflammatory exudate. Thus purified peritoneal exudate lymphocytes (PELs) are known to consist of over 90% T cells, and 59% of these cells bound aggregates. 10% of these Agg+ Ig- E-rosette+ cells were found in draining lymph node cell populations and none in thymus cell populations. The high frequency amongst PELs suggested that these Aggregate+ Ig- E-rosette+ cells might be activated T cells as these are known to occur in high proportion in PEL populations. Confirmatory evidence for this postulate was provided by the striking increase (from 10% to 46%) of Ig- E-rosette+ cells that bound aggregates when lymph node cells were activated by antigen stimulation in vitro.

Blocking the Expression of CD33 Enhances Chemotaxis of Activated T Lymphocytes Generated from AML Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3862-3862
Author(s):  
Rui-kun Zhong ◽  
Edward D. Ball
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Magnetic Beads ◽  
Immune Therapy ◽  
Biological Significance ◽  
Activated T Cells ◽  
Peptide Analog ◽  
Myeloid Antigens ◽  
Activated T Lymphocytes ◽  
Stromal Cell Derived Factor

Autologous T lymphocytes can be employed for immune therapy of patients with acute myeloid leukemia (AML). In an earlier study (Biol Blood Marrow Transplant2002; 8:557), we found that AML cells can be used as antigen presenting cells to activate and expand T cells in culture with IL-2 and monoclonal antibody (mAb) to CD3. In this study, we found that a substantial proportion of the expanded T cells expressed CD33 (34 ± 16%; range: 8 – 58%; N=11) and CD13 (26 ± 5%; range: 22 – 33%), but not CD14. It is unlikely that the myeloid markers were absorbed onto the activated T cells, since the same expression pattern was observed in cultures with purified T cells from normal donors. A literature review disclosed two reports that also observed co-expression of CD33 on activated T cells from both AML patients and normal controls (Schmidt-Wolf et al, Br J Haematol.1995; 90:512; Nakamura et al, letter in Blood, 1994; 83:1442). We measured the functional capacity of the activated T cells in a 4-hr Cr-51 release assay. Pre-incubation of the T cells with anti-CD33 mAb and/or anti-CD13 mAb did not change the cytotoxicity against AML cells. Also, killing of AML cells was not affected by the depletion of CD33+ or CD13+ activated T cells using magnetic beads. The activated T cells migrated in a chemotactic response to a peptide analog (CTCE-0214) of Stromal cell derived factor-1 (SDF-1) when measured in a trans-well assay. When activated T cells were pre-incubated with anti-CD33 mAb, enhanced chemotaxis was observed in response to CTCE-0214 (39.9 ± 0.5% vs 26.9 ± 0.3%, p < 0.001). However, incubation with anti-CD13 mAb did not change the proportion of chemotactic cells. The results of this study confirmed that myeloid antigens can be induced on activated T cells from patients with AML and that there are differences in the mobility of CD33+ T cells in the presence of a chemotactic molecule. Further study of the biological significance of CD33 expression on activated T cells in AML and other diseases is warranted.

HLA-G Transference From Multipotent Mesenchymal Stromal Cells to Activated T-Lymphocytes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3674-3674
Author(s):  
Rodrigo A Panepucci ◽  
Felipe Saldanha-Araujo ◽  
Kelen C R Malmegrim ◽  
Fabio M Oliveira ◽  
Patricia V B Palma ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Lymphocytes ◽  
Confocal Microscopy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Nuclear Staining ◽  
Activated T Cells ◽  
Activated T Lymphocytes ◽  
Membrane Bound

Abstract Abstract 3674 Poster Board III-610 HLA-G is a nonclassic human leukocyte antigen which is characterized by its limited variability, its highly tissue-specific expression and for its very distinct immunological role. Instead of triggering immune responses, HLA-G is exclusively inhibitory, suppressing immune cell functions. For instance, HLA-G is expressed by cells in sites considered immunologically privileged, such as the fetal cytotrophoblast, at the fetal–maternal interface, were it acts protecting the fetal tissue from the mother's immune response. HLA-G is also pathologically expressed in a diverse set of tumors, acting as an immunescape mechanism. Trough splicing mechanisms, HLA-G can be expressed as a membrane-bound or as a soluble isoform. Interestingly, the transference of membrane fragments between cells, a process called trogocytosis, can spread HLA-G inhibitory function beyond the reach of HLA-G-expressing cells. For instance, upon trogocytosis, effector CD4+ T cells stop proliferating, stop responding to stimulation, and behave as regulatory T cells. Recently, mesenchymal stromal cells (MSC) were shown to secrete soluble HLA-G, adding to the existing set of secreted molecules, by which MSC can modulate cells of the immune system. Despite the importance of secreted factors, cell-to-cell contacts have an important role in the immunological effects exerted by MSC. Based in these facts, we hypothesized that one of the mechanisms used by MSC to immunomodulate T cells, could involve trogocytosis mediated HLA-G transference. To test this, CD3+ T cell were immunomagnetically selected from peripheral blood mononuclear cells (PBMC) and pre-activated for 72hs using anti-CD2/CD3/CD28 beads. Activated T-cells were then incubated for 30 min, alone or with MSC. After this period, cells were recovered and the transfer of membrane bound molecules from MSC to T-cells was analyzed by flow cytometry (3 experiments) using antibodies against HLA-G. Confocal microscopy was carried in an additional experiment, using antibodies against HLA-G, CD140B (a specific MSC marker) and CD3. DAPI was used for nuclear staining. Flow cytometry analysis revealed that activated CD3+ T-cells did not express HLA-G, while MSC expressed HLA-G intracytoplasmatic. After 30 min of co-incubation, membrane bound HLA-G was detected in a variable percentage of CD3+ cells, ranging from 3 to up to 16%, characterizing the transfer of HLA-G from MSC to CD3+ T-cells. Confocal microscopy revealed that activated T-cells cultured alone did not stained for HLA-G or CD140B, while, about 12% of the CD3+ cells stained for membrane HLA-G, following the 30 min incubation with MSC. Additionally, CD140B was also transferred from MSC to CD3+ T-cells. These data are the first demonstration of trogocytosis mediated transfer of HLA-G from MSC to activated T lymphocytes. Given the significance of HLA-G expression and trogocytosis in normal and pathological situations, this newly described immunological mechanism should be considered in the development and application of MSC-based therapies. Supported by CNPq and FAPESP. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes.

1992 ◽  
Vol 176 (6) ◽  
pp. 1595-1604 ◽  
Author(s):  
P S Linsley ◽  
J L Greene ◽  
P Tan ◽  
J Bradshaw ◽  
J A Ledbetter ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Cell Adhesion ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Subsets ◽  
T Cell Proliferation ◽  
Activated T Cells ◽  
Activated T Lymphocytes ◽  
T Cell Adhesion

T cell costimulation by molecules on the antigen presenting cell (APC) is required for optimal T cell proliferation. The B7 molecule on APC binds the T lymphocyte receptor CD28, triggering increased interleukin 2 (IL-2) production and subsequent T cell proliferation. CTLA-4 is a predicted T cell membrane receptor homologous to CD28, which also binds the B7 counter receptor, but whose distribution and function are unknown. Here we have developed monoclonal antibodies (mAbs) specific for CTLA-4 and have investigated these questions. mAbs were produced that bound CTLA-4 but not CD28, and that blocked binding of CTLA-4 to B7. CTLA-4 expression as measured by these mAbs was virtually undetectable on resting T cells, but was increased several hundred-fold during T cell activation. On activated lymphocytes, CTLA-4 was expressed equally on CD4+ and CD8+ T cell subsets and was coexpressed with CD25, CD28, and CD45RO. CTLA-4 expression was lower than that of CD28, reaching a maximum of approximately 1/30-50 the level of CD28. Despite its lower expression, CTLA-4 was responsible for much of the B7 binding by large activated T cells. Anti-CTLA-4 mAb 11D4 and anti-CD28 mAb 9.3 acted cooperatively to inhibit T cell adhesion to B7, and to block T cell proliferation in primary mixed lymphocyte culture. When coimmobilized with anti T cell receptor (TCR) mAb, anti-CTLA-4 mAbs were less effective than anti-CD28 mAb 9.3 at costimulating proliferation of resting or activated T cells. However, coimmobilized combinations of anti-CD28 and anti-CTLA-4 were synergistic in their ability to augment anti-TCR-induced proliferation of preactivated CD4+ T cells. These results indicate that CTLA-4 is coexpressed with CD28 on activated T lymphocytes and cooperatively regulates T cell adhesion and activation by B7.

Prostaglandin E2 Plays a Key Role in the Immunosuppressive Properties of Adipose Tissue-Derived Mesenchymal Stromal Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3636-3636
Author(s):  
Rosa Yañez ◽  
Alberto Oviedo ◽  
Montserrat Aldea ◽  
Antonio Rubio ◽  
Juan A. Bueren ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cytokine Secretion ◽  
Activated T Cells ◽  
Expression Of Genes ◽  
Activated T Lymphocytes

Abstract Abstract 3636 Poster Board III-572 Mesenchymal stromal cells (MSCs) are multipotential non-hematopoietic cells that can be obtained from several tissues. These cells have a limited immunogenicity, and their immunosuppressive properties have led to their use to treat graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cells transplantation. In previous studies, we demonstrated that adipocyte tissue-derived MSCs (Ad-MSCs) suppress activated T cells proliferation and prevent GVHD in a haploidentical hematopoietic transplantation mouse model (Yañez, Stem Cells 2006). In the present study, we have investigated the mechanisms participating in the immunosuppressive properties of human Ad-MSCs. First, we confirmed that the addition of Ad-MSCs to activated T lymphocytes inhibited the production of pro-inflammatory cytokines (TNF-a, IFN-g, IL-6 and IL-12), and increased the secretion of the immunosuppressive IL-10. In these co-cultures, high levels of PGE2 were detected. The addition of indomethacin (IDM), an inhibitor of PGE2, restored the proliferation of activated T lymphocytes and increased the expression of genes related with proliferation. Furthermore, an increase in the expression of genes related with transcription factors and cytokines involved in the TH1/TH2 differentiation pathway of the activated T cells was detected. These results show that PGE2 plays a key role in the immunosuppressive effects of Ad-MSCs over activated T lymphocytes. Although, strikingly, the blockade of PGE2 by IDM did not restore the pro-inflammatory cytokine secretion profile in the Ad-MSCs/activated T lymphocytes co-cultures, the increase in the expression of activation and differentiation-related genes suggests a restoration, at an early time, of the cytokine secretion of the activated T lymphocytes. Analyses at different time-points after the addition of IDM are being conducted to confirm this hypothesis. When TGF-b was determined in these cultures, no changes were detected by the addition of Ad-MSCs to activated T lymphocytes cultures, showing that this factor does not account for the inhibitory effects of Ad-MSCs over activated T cells. Next, we studied the impact of Ad-MSCs over the maturation of dendritic cells. We generated immature myeloid (m-DCs) and plasmocytoid (p-DCs) dendritic cells, and induced their maturation with LPS. We found that in co-culture with Ad-MSCs, dendritic cells remained in an immature state, shown by decreased CD83 and CD80 expression, and by a decreased secretion of TNF-β by myeloid-DCs (m-DCs), and an increased production of IL-10 by plasmocytoid-DCs (p-DCs). The blockade by IDM of the PGE2 present in the co-cultures resulted in the maturation of p-DCs, but not of m-DCs, that remained in an immature state. These results show that PGE2 accounts for the immunosuppressive effects of Ad-MSCs over the maturation of p-DCs, but not over the maturation of m-DCs. Finally, when TGF-b1 was studied, no changes in the very low values of TGF-b levels were detected in the supernatants of m-DCs and p-DCs co-cultured Ad-MSCs, showing that this factor does not play an important role in the effects of Ad-MSCs on the maturation of m-DCs and p-DCs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Mildly oxidized low-density lipoproteins suppress the proliferation of activated CD4+ T-lymphocytes and their interleukin 2 receptor expression in vitro

1998 ◽  
Vol 330 (2) ◽  
pp. 659-666 ◽  
Author(s):  
Sylvie CASPAR-BAUGUIL ◽  
Majed SAADAWI ◽  
Anne NEGRE-SALVAYRE ◽  
Mogens THOMSEN ◽  
Robert SALVAYRE ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Clone ◽  
Peripheral Blood Lymphocytes ◽  
Cd4 T Cell ◽  
Activated T Cells ◽  
T Cell Clone ◽  
Activated T Lymphocytes

Activated T-lymphocytes are present in early atherosclerotic lesions where they may interact with oxidized low-density lipoproteins (oxLDLs). In this study the non-specific effect of oxLDLs on the activation of T-cells in vitro was investigated. LDLs were oxidized by UV irradiation and characterized by a low level of lipid peroxidation and only slight apolipoprotein B modification. Peripheral blood lymphocytes from normal individuals were stimulated in vitro with the polyclonal activator phytohaemagglutinin in the presence of various doses of LDLs and oxLDLs. LDLs enhanced the proliferation of peripheral blood lymphocytes at doses up to 100 μg/ml but were inhibitory at 200 μg/ml, whereas low doses of oxLDLs (over 10 μg/ml) inhibited the proliferation. OxLDLs also inhibited the proliferative responses of an alloreactive CD4+ T-cell line immortalized by Herpes virus saimiri and an influenza haemagglutinin-specific CD4+ T-cell clone. Viability tests using Trypan Blue exclusion or expression of Apo2.7, an apoptosis marker, did not indicate any significant cell death at doses up to 100 μg/ml oxLDL. At this concentration, cell-cycle analysis showed an accumulation of cells at the G1/S interface in the CD4+ cell clone, without significant DNA fragmentation. The expression of the activation antigen CD25 on T-lymphocytes (on phytohaemagglutinin-activated T-cells and on CD4+ T-cell clone), requisite to the commitment of activated T-cells from G1 phase to S phase, was also inhibited by oxLDLs whereas expression of other activation antigens such as CD69 and HLA-DR was unchanged. In conclusion, these data show that mildly oxidized LDLs inhibit the proliferation and CD25 expression of activated T-lymphocytes and suggest that oxLDLs may slow down the T-cell response in atherosclerotic lesions.

scholarly journals L-Selectin Shedding Does Not Regulate Constitutive T Cell Trafficking but Controls the Migration Pathways of Antigen-activated T Lymphocytes

2003 ◽  
Vol 198 (9) ◽  
pp. 1323-1335 ◽  
Author(s):  
Elena Galkina ◽  
Kyriakos Tanousis ◽  
Graham Preece ◽  
Mauro Tolaini ◽  
Dimitris Kioussis ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mutant Form ◽  
Cell Trafficking ◽  
Lymphocyte Migration ◽  
High Endothelial Venules ◽  
Activated T Cells ◽  
Activated T Lymphocytes ◽  
Migration Pathways

L-Selectin mediates rolling of lymphocytes in high endothelial venules (HEVs) of peripheral lymph nodes (PLNs). Cross-linking of L-selectin causes proteolytic shedding of its ectodomain, the physiological significance of which is unknown. To determine whether L-selectin shedding regulates lymphocyte migration, a mutant form that resists shedding (LΔP-selectin) was engineered. Transgenic mice expressing either LΔP or wild-type (WT) L-selectin on T cells were crossed with L-selectin knockout (KO) mice. The cellularity and subset composition of secondary lymphoid organs did not differ between LΔP and WT mice, however, they were different from C57BL/6. Plasma levels of soluble L-selectin in LΔP mice were reduced to &lt;5% of WT and C57BL/6 mice. The rolling properties of T lymphocytes from LΔP and WT mice on immobilized L-selectin ligands were similar. Furthermore, similar numbers of LΔP and WT T lymphocytes were recruited from the bloodstream into PLNs in mice, although LΔP T cells transmigrated HEVs more slowly. WT, but not LΔP-selectin, underwent rapid, metalloproteinase-dependent shedding after TCR engagement, and LΔP T cells retained the capacity to enter PLNs from the bloodstream. These results suggest that the ability to shed L-selectin is not required for T cell recirculation and homing to PLNs. However, L-selectin shedding from antigen-activated T cells prevents reentry into PLNs.

scholarly journals Turnover of T Cells in Murine Gammaherpesvirus 68-Infected Mice

1999 ◽  
Vol 73 (9) ◽  
pp. 7866-7869 ◽  
Author(s):  
Ann Marie Hamilton-Easton ◽  
Jan P. Christensen ◽  
Peter C. Doherty
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Virus Infection ◽  
Peripheral Blood ◽  
Virus Challenge ◽  
Murine Gammaherpesvirus ◽  
Activated T Lymphocytes ◽  
Gammaherpesvirus 68 ◽  
Respiratory Challenge ◽  
Murine Gammaherpesvirus 68

ABSTRACT Respiratory challenge of C57BL/6 mice with murine gammaherpesvirus 68 induces proliferation of T lymphocytes early after infection, as evidenced by incorporation of the DNA precursor bromodeoxyuridine. Using pulse-chase analysis, splenic and peripheral blood activated T lymphocytes were found to continue dividing for at least a month after the initial virus challenge. The results are in accord with the idea that T cells are stimulated for a substantial time after the acute, lytic phase of virus infection is resolved.

Bortezomib Induces Selective Depletion of Activated T Lymphocytes and Modifies the Cytokine’s Production Pattern.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 615-615
Author(s):  
Belen Blanco ◽  
Jose A. Perez-Simon ◽  
Luis I. Sanchez-Abarca ◽  
Xonia Carvajal-Vergara ◽  
Juan Mateos ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Activated T Cells ◽  
Alloreactive T Cells ◽  
Lymphocyte Cultures ◽  
Activated T Lymphocytes ◽  
Mixed Lymphocyte Cultures

Abstract The NF-kB family has emerged as a key transducer of inflammatory signals involved in dendritic cell maturation and T lymphocyte activation. Accordingly, the diverse signaling pathways downstream of TCR/CD3 converge on several transcription factors including NFAT, AP-1 and NF-kB. We explored the ability of the proteosome inhibitor bortezomib, which prevents Nuclear Factor kB (NF-kB) activation, to block T-cell activation, proliferation and survival within alloreactive as compared to resting T-cells. For this purpose, T-cells were stimulated with PHA, aCD3/aCD28, allogeneic dendritic cells (APC) or through mixed lymphocyte cultures. NF-kB expression increased in activated T-lymphocytes as compared to resting T-cells. Interestingly, the higher the NF-kB expression, the more intense the proliferative blockade induced by bortezomib. This effect on proliferation was due to a selective induction of apoptosis among activated T-cells. Thus, after mixed lymphocyte reaction (MLR) cultures, alloreactive T-cells were 2 logs more sensitive to bortezomib-induced apoptosis than the resting T-cell counterpart as assessed by annexin / 7AAD staining. This effect of bortezomib was partially blocked by adding the caspase inhibitor Z-VAD to the culture. The addition of bortezomib not only decreased the proliferation and viability of activated T-lymphocytes but also the levels of IFN-g and IL-2, which were significantly decreased among activated T-cells cultured with bortezomib at doses ranging from 10 to 100 nM. Secondary mixed lymphocyte cultures demonstrated a selective loss of alloreactive T-cells while activation and proliferation against third party donor was partially preserved. In conclusion, at concentrations reached in the clinical setting, bortezomib induces selective apoptosis and decreases Th1 response among alloreactive T-lymphocytes while it barely affects unstimulated T-cells. These results establish the basis for the clinical use of bortezomib in the management of GVHD

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