scholarly journals Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation

2017 ◽  
Vol 18 (7) ◽  
pp. 1603 ◽  
Author(s):  
Anne Louise Schacht Revenfeld ◽  
Rikke Bæk ◽  
Malene Møller Jørgensen ◽  
Kim Varming ◽  
Allan Stensballe
Keyword(s):  
T Cells ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Hla Dr ◽  
Regulatory Phenotype

scholarly journals Idiotype-like determinants on human T lymphocytes alloactivated in mixed lymphocyte culture.

1982 ◽  
Vol 156 (1) ◽  
pp. 283-288 ◽  
Author(s):  
N Suciu-Foca ◽  
C Rohowsky ◽  
P Kung ◽  
D W King
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Mixed Lymphocyte Culture ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocyte Culture ◽  
Lymphocyte Response ◽  
Hla Dr ◽  
T Lymphoblasts

T cells alloactivated in 5-d MLC with an HLA-DR-different stimulator acquire the capacity of stimulating the autologous mixed lymphocyte response (AMLR). We have demonstrated that activation of AMLR by allosensitized T cells is determined by the expression of the idiotype receptor for the stimulating HLA-DR alloantigen. This has been shown in experiments in which purified, OKT-3-positive T cell suspensions were first primed for 9 d with AMLR-activated T lymphoblasts, then tested in secondary AMLR with autologous lymphoblasts sensitized to various HLA-DR alloantigens. Accelerated memory responses were induced only by autologous lymphoblasts that had been sensitized against the same HLA-DR specificity as the primary AMLR stimulators. This response was not inhibited by a mouse monoclonal antibody recognizing Ia-like determinants, and was not triggered by human allogeneic resting peripheral blood lymphocytes. Thus, recognition of alloactivated T lymphoblasts in secondary AMLR seems to be specific for the idiotype-like determinants expressed by the autologous stimulators.

scholarly journals POS0673 TOLEROGENIC DENDRITIC CELLS IN RHEUMATOID ARTHRITIS PATIENTS: NEWS AND PROMISES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 581.2-581
Author(s):  
Y. Kurochkina ◽  
E. Chernykh ◽  
A. Sizikov
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Dendritic Cells ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Moderate Activity ◽  
Blood Monocytes ◽  
Gm Csf ◽  
Hla Dr ◽  
Enhanced Expression

Background:Dendritic cells (DCs) are known to contribute to the pathogenesis of rheumatoid arthritis (RA) through presentation of cartilage glycoprotein, production of proinflammatory cytokines and activation of Th1/Th17 responses. Along with stimulating activity, DCs may exhibit suppressive functions via capacity to induce T cell apoptosis/anergy and to generate regulatory T cells. Since these DCs have potential to control autoreactive T-lymphocytes, the enhancing of tolerogenic properties of DCs seems to be a new important strategy in treatment of RA. Dexamethasone is widely used in clinical practice and can be used as a tolerogenic substance. Therefore, the properties of DCs generated in presence of dexamethasone are of great clinical interests.Objectives:The aim of our study is to describe the properties of tolerogenic DCs, generated with dexamethasone in patients with RA and their influence on autologous T-cells.Methods:Sixty five patients with RA with high and moderate activity of disease were recruited in this study. All patients follow ACR/EULAR criteria (2010). All studies were performed after receiving informed consent. All patients received conventional synthetic DMARDs. DCs were generated from blood monocytes culturing for 5 days with GM-CSF and IFN-α in the presence dexamethasone (dexDCS), applied on third day. LPS as maturation stimuli was added on fourth day. The expression of CD14, CD83, HLA-DR, TLR-2 on the surface of DCs was measured by flow cytometry. The functions of DCs were evaluated by measuring cytokine production and DCs allostimulatory activity in mixed lymphocyte culture. Mature DCs generated in absence of dexamethasone used as control.Results:We revealed that dexDCs are characterized by enhanced expression of CD14+cells and decreased number of CD83+cells but percent of HLA-DR+cells were constant (about 85). DexDCs show high expression of TLR-2 is seen as tolerogenic molecule (75%vs51%, p=0.05 compared to control). DexDCs also have marked prominent increase of TNFα/IL-10 ratio in contrast to control (0.59 vs 1.8, p=0.03). DexDCs suppressed proliferation of allogenic T-cells (2005 vs 7980 cpm, p=0.0002). To assess the stability of the DC in the proinfflamatory micro-environment after assessing stimulatory activity dexDCs were then cultivated with LPS and allostimulatory activity were evaluated one more. The stimulation activity dexDCs after incubation with LPS were not increase (4692 vs 6053 cpm, p=0.7). Also earlier we showed possibility of dexDCs induse apoptosis of autologous T-cells, activation of CD4+IL10+Tr1 and possession of antigen-specific suppression.Conclusion:The data obtained indicate that dexDCs from RA patients have the main tolerogenic features and stable in inflammatory environment that proves their potential in the treatment of rheumatoid arthritis.Disclosure of Interests:None declared

scholarly journals Contribution of direct and indirect recognition pathways to T cell alloreactivity.

1993 ◽  
Vol 177 (6) ◽  
pp. 1643-1650 ◽  
Author(s):  
Z Liu ◽  
Y K Sun ◽  
Y P Xi ◽  
A Maffei ◽  
E Reed ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Indirect Pathway ◽  
Hla Dr ◽  
Indirect Allorecognition ◽  
Antigen Presenting ◽  
Direct Recognition

T cells from an HLA-DR11/DR12 responder were stimulated in mixed lymphocyte culture with cells carrying the DR1 antigen. After priming, T cells proliferated in response to both DR1-positive-stimulating cells and a peptide derived from a polymorphic region of the HLA-DR beta 1*0101 chain presented by responder's antigen-presenting cells (APC). The dominant epitope recognized by the primed T cells corresponded to residue 21-42 and was presented by the responder's HLA-DR12 antigen. The DR1 peptide-reactive T cells express T cell receptor V beta 3. The results demonstrate that allopeptides derived from the processing and presentation of donor major histocompatibility complex molecules by host-derived APC trigger alloreactivity. The frequency of T cells engaged in the indirect pathway of allorecognition is about 100-fold lower than that of T cells participating in the direct recognition of native HLA-DR antigen. However, indirect allorecognition may play an important role in chronic allograft rejection, a phenomenon that is mediated by the activation of T helper cells and of alloantibody-producing B cells.

scholarly journals Sequential responses of mouse spleen T cells in mixed lymphocyte culture-induced cytolysis.

1975 ◽  
Vol 141 (2) ◽  
pp. 508-512 ◽  
Author(s):  
P Häyry ◽  
L C Andersson
Keyword(s):  
T Cells ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Mouse Spleen ◽  
Blast Transformation

T cells triggered to blast transformation and proliferation by histoincompatible cells have the capacity of reverting "back" to lymphocytes. These "secondary" lymphocytes and their progeny cells are able to respond repeatedly to the same allogeneic stimulus in vitro.

scholarly journals Haplotype-specific suppression of cytotoxic T cell induction by antigen inappropriately presented on T cells.

1983 ◽  
Vol 157 (1) ◽  
pp. 141-154 ◽  
Author(s):  
P J Fink ◽  
I L Weissman ◽  
M J Bevan
Keyword(s):  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Cytotoxic T Cell ◽  
Spleen Cells ◽  
Specific Suppression ◽  
Veto Cells

To detect a strong cytotoxic T lymphocyte (CTL) response to minor histocompatibility (H) antigens in a 5-d mixed lymphocyte culture, it is necessary to use a responder that has been primed in vivo with antigen-bearing cells. It has previously been shown that minor-H-specific CTL can be primed in vivo both directly by foreign spleen cells and by presentation of foreign minor H antigens on host antigen-presenting cells. This latter route is evident in the phenomenon of cross-priming, in which H-2 heterozygous (A x B)F1 mice injected 2 wk previously with minor H-different H-2A (A') spleen cells generate both H-2A- and H-2B-restricted minor-H-specific CTL. In a study of the kinetics of direct- vs. cross-priming to minors in F1 mice, we have found that minor H-different T cells actually suppress the induction of virgin CTL capable of recognizing them. CTL activity measured from F1 mice 3-6 d after injection with viable A' spleen cells is largely H-2B restricted. The H-2A-restricted response recovers such that roughly equal A- and B-restricted activity is detected in mice as early as 8-10 d postinjection. This temporary hyporeactivity does not result from generalized immunosuppression--it is specific for those CTL that recognize the foreign minor H antigen in the context of the H-2 antigens on the injected spleen cells. The injected spleen cells that mediate this suppression are radiosensitive T cells; Lyt-2+ T cells are highly efficient at suppressing the induction of CTL in vivo. No graft vs. host reaction by the injected T cells appears to be required, as suppression of direct primed CTL can be mediated by spleen cells that are wholly tolerant of both host H-2 and minor H antigens. Suppression cannot be demonstrated by in vitro mixing experiments. Several possible mechanisms for haplotype-specific suppression are discussed, including inactivation of responding CTL by veto cells and in vivo sequestration of responding CTL by the injected spleen cells.

scholarly journals Autologous mixed lymphocyte culture reactions and generation of cytotoxic T cells.

1977 ◽  
Vol 146 (6) ◽  
pp. 1809-1814 ◽  
Author(s):  
R A Vande Stouwe ◽  
H G Kunkel ◽  
J P Halper ◽  
M E Weksler
Keyword(s):  
T Cells ◽  
Cell Lines ◽  
Lymphoid Cell ◽  
Cytotoxic T Cells ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Cell Generation ◽  
Cytotoxic T Cell ◽  
Cytotoxic Cells ◽  
Lymphoid Cell Lines

Autologous mixed lymphocyte culture (MLC) reactions were studied utilizing autologous purified B cells and autologous established B lymphoid cell lines as stimulating cells. Similar results were obtained although somewhat greater stimulation of lymphocyte proliferation was found with the autologous lymphoid cell lines. Cytotoxic T cells were not generated against the stimulating cells in either case when peripheral blood cells were used as targets. A low cytotoxicity was detected when lymphoid cell lines were used both as stimulators and target cells. However this was nonspecific and was always greater for heterologous lines than for the stimulator line. Third-party cell experiments demonstrated that the autologous reaction could serve as a proliferative stimulus for specific cytotoxic lymphocyte generation. Heat-treated allogeneic lymphocytes that alone do not stimulate proliferation ro cytotoxic T-cell generation in MLC reactions when added to the autologous system produced specific cytotoxic cells. The separation of the proliferative phase from the cytotoxic cell generation was especially striking in these experiments. Possible uses of this system for the generation of specific cytotoxic cells to other nonstimulatory cells are discussed.

scholarly journals Phenotypic characterization of human cytolytic T lymphocytes in mixed lymphocyte culture.

1981 ◽  
Vol 153 (1) ◽  
pp. 213-218 ◽  
Author(s):  
A Moretta ◽  
M C Mingari ◽  
B F Haynes ◽  
R P Sekaly ◽  
L Moretta ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Mixed Lymphocyte Reaction ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Phenotypic Characterization ◽  
Cytolytic T Lymphocytes ◽  
Activated T Cells

Mixed lymphocyte reaction (MLR)-activated T cells were analyzed according to the expression of various cell surface markers by the specific cytotoxic T lymphocytes (CTL) generated in the MLR. CTL were found exclusively in a population of MLR-activated T cells that lacked detectable Fc gamma R but that expressed a surface antigen recognized by the 4F2 monoclonal antibody. In contrast, CTL were found in both the Ia-positive and Ia-negative cells after MLR activation. Thus, the specific CTL generated in the allogeneic MLR can be identified and isolated by virtue of the expression of a particular cell surface marker.

scholarly journals Study of the cells proliferating in parent versus F hybrid mixed lymphocyte culture.

1975 ◽  
Vol 141 (4) ◽  
pp. 775-787 ◽  
Author(s):  
P F Piguet ◽  
H K Dewey ◽  
P Vassalli
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Lymphocytes ◽  
Hybrid Cell ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Lymphoid Cells ◽  
Spleen Cells ◽  
F1 Hybrid ◽  
Proliferation And Differentiation

Caryotypic analysis of the cells dividing in mouse parent-hybrid MLC showed an F1 hybrid cell proliferation, which varied depending upon the source of lymphoid cells used: strong in spleen MLC (sometimes equal to that of the parental cells), less marked in lymph node cell MLC, and most often absent in MLC between cortisone-resistant (CR) thymocytes. MLC between parental spleen cells and F1 CR thymocytes showed, however, that in certain conditions of culture F thymocytes can also proliferate. Using parental or F1 spleen cells lacking T lymphocytes, it was found that F1 cell proliferation is entirely dependent upon the presence of parental T cells, but does not require the presence of T lymphocytes among the F1 cells. Immunofluorescence analysis of the blasts observed in one-way MLC showed that about 70% of the parental blasts were T blasts, and 25%B blasts (containing a high proportion of plasmablasts); among the F1 blasts, there was also the same percentage of B blasts and plasmablasts, but many of the T blasts bore only small amounts of T-cell antigen (MTLA), and there was also about 20%of unstained blasts, possibly T blasts bearing MTLA in amounts undetectable by immunofluorescence. The possibility is discussed that the F1 responding T cells belong to a subpopulation performing a suppressive function; MLC lacking F1 T cells showed increased [3H] thymidine incorporation. The proliferation and differentiation of parental and F1 B cells may result mainly from an unspecific, "polyclonal" triggering.

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