scholarly journals Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Da Som Kim ◽  
Youngjae Park ◽  
Jeong-Won Choi ◽  
Sung-Hwan Park ◽  
Mi-La Cho ◽  
...  
Keyword(s):  
T Cell ◽  
Combination Therapy ◽  
Combination Treatment ◽  
Lactobacillus Acidophilus ◽  
Therapeutic Efficacy ◽  
Cell Subset ◽  
Treg Cells ◽  
T Cell Subsets ◽  
T Cell Subset

ObjectiveTacrolimus (Tac) is an immunosuppressant used in the treatment of systemic lupus erythematosus (SLE); however, it induces T cell subset imbalances by reducing regulatory T (Treg) cells. Lactobacillus acidophilus (LA) is reported to have therapeutic efficacy in immune-mediated diseases via T cell regulation.MethodsThis study investigated whether a combination therapy of LA and Tac improves the therapeutic efficacy of Tac by modulating T cell subset populations in an animal model of SLE. Eight-week-old MRL/lpr mice were orally administered with 5 mg/kg of Tac and/or 50 mg/kg of LA daily for 8 weeks. Cecal microbiota compositions, serum autoantibodies levels, the degree of proteinuria, histological changes in the kidney, and populations of various T cell subsets in the spleen were analyzed.ResultsMice presented with significant gut dysbiosis, which were subsequently recovered by the combination treatment of Tac and LA. Double negative T cells in the peripheral blood and spleens of MRL/lpr mice were significantly decreased by the combination therapy. The combination treatment reduced serum levels of anti-dsDNA antibodies and Immunoglobulin G2a, and renal pathology scores were also markedly alleviated. The combination therapy induced Treg cells and decreased T helper 17 (Th17) cells both in vitro and in vivo. In vitro treatment with LA induced the production of indoleamine-2,3-dioxygenase, programmed death-ligand 1, and interleukin-10 via the specific intracellular adhesion molecule-3 grabbing non-integrin homolog-related 3 receptor signals.ConclusionThe present findings indicate that LA augments the therapeutic effect of Tac and modulates Th17/Treg balance in a murine model of SLE.

Lactobacillus Acidophilus Supplementation Exerts A Synergistic Effect on Tacrolimus Efficacy by Restoring Th17/Treg Imbalance in Lupus-Prone Mice via the SIGNR3 Pathway

2020 ◽  
Author(s):  
Da Som Kim ◽  
Youngjae Park ◽  
Jeong-Won Choi ◽  
Sung-Hwan Park ◽  
MI-LA CHO ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Combination Therapy ◽  
Combination Treatment ◽  
Lupus Erythematosus ◽  
Lactobacillus Acidophilus ◽  
Therapeutic Efficacy ◽  
T Cell Subsets ◽  
Systemic Autoimmune Disease

Abstract Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by tissue-binding autoantibodies and immune complexes. Tacrolimus (Tac), also known as FK506, is an immunosuppressant used in the treatment of lupus; however, it induces T-cell imbalances. Lactobacillus acidophilus (LA) is reported to have therapeutic efficacy in immune-mediated diseases via T-cell regulation. This study investigated whether a combination therapy of LA and Tac improves the therapeutic efficacy of Tac by ameliorating T-cell imbalance in an animal model of SLE. Eight-week-old MRL/Mp-Faslpr (MRL/lpr) mice were orally administered with 5 mg/kg of Tac and/or 50 mg/kg of LA daily for 8 weeks. Caecal microbiota compositions, serum autoantibodies levels, the degree of proteinuria, histological changes in the kidney, and populations of various T-cell subsets in the spleen were analysed. Results: MRL/lpr mice presented with significant gut microbiota imbalances, which were subsequently recovered by the combination treatment of Tac and LA. Double negative T-cells, a pathogenic subset of T-cells, in the peripheral blood and spleens of MRL/lpr mice were significantly decreased by the combination therapy. The combination treatment also reduced serum levels of anti-double-stranded DNA antibodies and immunoglobulin G2a, and renal pathology scores were markedly alleviated. The combination therapy induced Treg cells and decreased Th17 cells both in vitro and in vivo. In vitro treatment with LA induced the production of indoleamine-2,3-dioxygenase, programmed death-ligand 1, and inerleukin-10, which was partially mediated by the induction of the specific intracellular adhesion molecule-3 grabbing non-integrin homolog-related 3 (SIGNR3) receptor. Conclusions: The present findings indicate that LA augments the therapeutic effect of Tac and restores Th17/Treg balance in a murine model of lupus. Accordingly, the combination treatment of Tac with LA could be a promising therapeutic candidate for lupus.

scholarly journals Dimethyl fumarate–induced lymphopenia in MS due to differential T-cell subset apoptosis

2017 ◽  
Vol 4 (3) ◽  
pp. e340 ◽  
Author(s):  
Mahtab Ghadiri ◽  
Ayman Rezk ◽  
Rui Li ◽  
Ashley Evans ◽  
Felix Luessi ◽  
...  
Keyword(s):  
T Cell ◽  
Apoptotic Cell ◽  
Cell Subset ◽  
Dimethyl Fumarate ◽  
T Cell Subsets ◽  
T Cell Subset ◽  
Cell Counts ◽  
Induced Apoptosis

Objective:To examine the mechanism underlying the preferential CD8+ vs CD4+ T-cell lymphopenia induced by dimethyl fumarate (DMF) treatment of MS.Methods:Total lymphocyte counts and comprehensive T-cell subset analyses were performed in high-quality samples obtained from patients with MS prior to and serially following DMF treatment initiation. Random coefficient mixed-effects analysis was used to model the trajectory of T-cell subset losses in vivo. Survival and apoptosis of distinct T-cell subsets were assessed following in vitro exposure to DMF.Results:Best-fit modeling indicated that the DMF-induced preferential reductions in CD8+ vs CD4+ T-cell counts nonetheless followed similar depletion kinetics, suggesting a similar rather than distinct mechanism involved in losses of both the CD8+ and CD4+ T cells. In vitro, DMF exposure resulted in dose-dependent reductions in T-cell survival, which were found to reflect apoptotic cell death. This DMF-induced apoptosis was greater for CD8+ vs CD4+, as well as for memory vs naive, and conventional vs regulatory T-cell subsets, a pattern which mirrored preferential T-cell subset losses that we observed during in vivo treatment of patients.Conclusions:Differential apoptosis mediated by DMF may underlie the preferential lymphopenia of distinct T-cell subsets, including CD8+ and memory T-cell subsets, seen in treated patients with MS. This differential susceptibility of distinct T-cell subsets to DMF-induced apoptosis may contribute to both the safety and efficacy profiles of DMF in patients with MS.

scholarly journals Reconstitution of T Cell Subsets Following Allogeneic Hematopoietic Cell Transplantation

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1974 ◽  
Author(s):  
Linde Dekker ◽  
Coco de Koning ◽  
Caroline Lindemans ◽  
Stefan Nierkens
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
T Cell ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cell Subset ◽  
Γδ T Cells ◽  
Hematopoietic Cell ◽  
T Cell Subsets ◽  
T Cell Subset

Allogeneic (allo) hematopoietic cell transplantation (HCT) is the only curative treatment option for patients suffering from chemotherapy-refractory or relapsed hematological malignancies. The occurrence of morbidity and mortality after allo-HCT is still high. This is partly correlated with the immunological recovery of the T cell subsets, of which the dynamics and relations to complications are still poorly understood. Detailed information on T cell subset recovery is crucial to provide tools for better prediction and modulation of adverse events. Here, we review the current knowledge regarding CD4+ and CD8+ T cells, γδ T cells, iNKT cells, Treg cells, MAIT cells and naive and memory T cell reconstitution, as well as their relations to outcome, considering different cell sources and immunosuppressive therapies. We conclude that the T cell subsets reconstitute in different ways and are associated with distinct adverse and beneficial events; however, adequate reconstitution of all the subsets is associated with better overall survival. Although the exact mechanisms involved in the reconstitution of each T cell subset and their associations with allo-HCT outcome need to be further elucidated, the data and suggestions presented here point towards the development of individualized approaches to improve their reconstitution. This includes the modulation of immunotherapeutic interventions based on more detailed immune monitoring, aiming to improve overall survival changes.

scholarly journals In situ quantitation of lymph node helper, suppressor, and cytotoxic T cell subsets in AIDS

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 596-603 ◽  
Author(s):  
GS Wood ◽  
BF Burns ◽  
RF Dorfman ◽  
RA Warnke
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Germinal Center ◽  
Feedback Inhibition ◽  
Cell Subset ◽  
Suppressor Cells ◽  
T Cell Subsets ◽  
Cytotoxic T Cell ◽  
B Cell Differentiation ◽  
T Cell Subset

Abstract We have used the novel monoclonal antibodies 9.3 and anti-Leu-8 in conjunction with other T cell markers to quantify T cell subpopulations in the paracortex, mantle, and germinal center compartments of frozen sections of lymph nodes from seven homosexual men with acquired immunodeficiency syndrome (AIDS) and five heterosexual controls. Antibody 9.3 allows dissection of the Leu-2+ cytotoxic/suppressor subset (Tcs) into 9.3+ cytotoxic cells (Tc) and 9.3- suppressor cells (Ts). Anti-Leu-8 allows dissection of the Leu-3+ helper subset (TH) into functionally distinct subpopulations. The data indicate that the T cells in patients with AIDS exhibit normal antigen expression but altered subset ratios. In this series, the data suggested that the reversal of the paracortical TH-Tcs ratio was due to an increase in Ts with a concomitant decrease in TH and Tc. These changes were also reflected in a reversal of the normal paracortical Tc-Ts ratio (3.0) to less than 1.0. Furthermore, the data suggested a marked decrease in paracortical Leu-3+8+TH, which are known to have inducer function in cellular immune reactions and exert feedback inhibition of immunoglobulin production through a suppressor T cell intermediary. In contrast, there was preservation of the Leu-3+8-TH population within the germinal center. This T cell subset is known to help B cell differentiation. This microenvironmentally specific constellation of T cell subset alterations within lymph nodes may in part explain several of the immunologic findings associated with AIDS.

scholarly journals Cytotoxic Activity and Memory T Cell Subset Distribution of in vitro-Stimulated CD8+ T Cells Specific for HER2/neu Epitopes

2019 ◽  
Vol 10 ◽  
Author(s):  
Maria Kuznetsova ◽  
Julia Lopatnikova ◽  
Julia Shevchenko ◽  
Alexander Silkov ◽  
Amir Maksyutov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic Activity ◽  
Cd8 T Cells ◽  
Cell Subset ◽  
T Cell Subset ◽  
Memory T Cell ◽  
Subset Distribution

scholarly journals Phenotypic and Functional Separation of Memory and Effector Human CD8+ T Cells

1997 ◽  
Vol 186 (9) ◽  
pp. 1407-1418 ◽  
Author(s):  
Dörte Hamann ◽  
Paul A. Baars ◽  
Martin H.G. Rep ◽  
Berend Hooibrink ◽  
Susana R. Kerkhof-Garde ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Fas Ligand ◽  
Cytotoxic T Lymphocyte ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
Cytolytic Activity ◽  
T Cell Subset

Human CD8+ memory- and effector-type T cells are poorly defined. We show here that, next to a naive compartment, two discrete primed subpopulations can be found within the circulating human CD8+ T cell subset. First, CD45RA−CD45R0+ cells are reminiscent of memory-type T cells in that they express elevated levels of CD95 (Fas) and the integrin family members CD11a, CD18, CD29, CD49d, and CD49e, compared to naive CD8+ T cells, and are able to secrete not only interleukin (IL) 2 but also interferon γ, tumor necrosis factor α, and IL-4. This subset does not exert cytolytic activity without prior in vitro stimulation but does contain virus-specific cytotoxic T lymphocyte (CTL) precursors. A second primed population is characterized by CD45RA expression with concomitant absence of expression of the costimulatory molecules CD27 and CD28. The CD8+CD45RA+CD27− population contains T cells expressing high levels of CD11a, CD11b, CD18, and CD49d, whereas CD62L (L-selectin) is not expressed. These T cells do not secrete IL-2 or -4 but can produce IFN-γ and TNF-α. In accordance with this finding, cells contained within this subpopulation depend for proliferation on exogenous growth factors such as IL-2 and -15. Interestingly, CD8+CD45RA+CD27− cells parallel effector CTLs, as they abundantly express Fas-ligand mRNA, contain perforin and granzyme B, and have high cytolytic activity without in vitro prestimulation. Based on both phenotypic and functional properties, we conclude that memory- and effector-type T cells can be separated as distinct entities within the human CD8+ T cell subset.

scholarly journals Phenotypical and Functional Analysis of Intraepithelial Lymphocytes from Small Intestine of Mice in Oral Tolerance

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Maristela Ruberti ◽  
Luis Gustavo Romani Fernandes ◽  
Patricia Ucelli Simioni ◽  
Dirce Lima Gabriel ◽  
Áureo Tatsumi Yamada ◽  
...  
Keyword(s):  
Small Intestine ◽  
T Cell ◽  
Oral Tolerance ◽  
Cell Subset ◽  
Intraepithelial Lymphocytes ◽  
T Cell Subsets ◽  
T Cell Subset ◽  
Small Intestines ◽  
And Function ◽  
Lower Expression

In this work, we evaluated the effects of administration of OVA on phenotype and function of intraepithelial lymphocytes (IELs) from small intestine of transgenic (TGN) DO11.10 and wild-type BALB/c mice. While the small intestines from BALB/c presented a well preserved structure, those from TGN showed an inflamed aspect. The ingestion of OVA induced a reduction in the number of IELs in small intestines of TGN, but it did not change the frequencies of CD8+and CD4+T-cell subsets. Administration of OVA via oral + ip increased the frequency of CD103+cells in CD4+T-cell subset in IELs of both BALB/c and TGN mice and elevated its expression in CD8β+T-cell subset in IELs of TGN. The frequency of Foxp3+cells increased in all subsets in IELs of BALB/c treated with OVA; in IELs of TGN, it increased only in CD25+subset. IELs from BALB/c tolerant mice had lower expression of all cytokines studied, whereas those from TGN showed high expression of inflammatory cytokines, especially of IFN-γ, TGF-β, and TNF-α. Overall, our results suggest that the inability of TGN to become tolerant may be related to disorganization and altered proportions of inflammatory/regulatory T cells in its intestinal mucosa.

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