scholarly journals CD86+ or HLA-G+ can be transferred via trogocytosis from myeloma cells to T cells and are associated with poor prognosis

Blood ◽  
2012 ◽  
Vol 120 (10) ◽  
pp. 2055-2063 ◽  
Author(s):  
Ross Brown ◽  
Karieshma Kabani ◽  
James Favaloro ◽  
Shihong Yang ◽  
P. Joy Ho ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Poor Prognosis ◽  
Plasma Cells ◽  
Side Population ◽  
Immune Surveillance ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Leukocyte Antigen

Abstract The transfer of membrane proteins between cells during contact, known as trogocytosis, can create novel cells with a unique phenotype and altered function. We demonstrate that trogocytosis is more common in multiple myeloma (MM) than chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia; that T cells are more probable to be recipients than B or natural killer cells; that trogocytosis occurs independently of either the T-cell receptor or HLA compatibility; and that after trogocytosis, T cells with acquired antigens can become novel regulators of T-cell proliferation. We screened 168 patients with MM and found that CD86 and human leukocyte antigen G (HLA-G) were antigens commonly acquired by T cells from malignant plasma cells. CD3+CD86acq+ and CD3+ HLA-Gacq+ cells were more prevalent in bone marrow than peripheral blood samples. The presence of either CD86 or HLA-G on malignant plasma cells was associated with a poor prognosis. CD38++ side population cells expressed HLA-G, suggesting that these putative myeloma stem cells could generate immune tolerance. HLA-G+ T cells had a regulatory potency similar to natural Tregs, thus providing another novel mechanism for MM to avoid effective immune surveillance.

scholarly journals 200. Generation of CAR-T Cells Lacking T Cell Receptor and Human Leukocyte Antigen Using Engineered Meganucleases

2016 ◽  
Vol 24 ◽  
pp. S78 ◽  
Author(s):  
Christina Pham ◽  
Aaron Martin ◽  
Jeyaraj Antony ◽  
Daniel MacLeod ◽  
Audrey Brown ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Leukocyte Antigen ◽  
T Cell Receptor ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Leukocyte Antigen ◽  
Car T Cells ◽  
Car T

scholarly journals T cell receptor V-segment frequencies in peripheral blood T cells correlate with human leukocyte antigen type.

1991 ◽  
Vol 174 (5) ◽  
pp. 1139-1146 ◽  
Author(s):  
B Gulwani-Akolkar ◽  
D N Posnett ◽  
C H Janson ◽  
J Grunewald ◽  
H Wigzell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Leukocyte Antigen ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Class I ◽  
Sibling Pairs ◽  
Leukocyte Antigen

We compared T cell receptor (TCR) V-segment frequencies in human leukocyte antigen (HLA) identical siblings to sibling pairs who differ at one or both HLA haplotypes using four V beta-specific and one V alpha-specific monoclonal antibody. In every one of nine families HLA-identical sibs had the most similar patterns of V-segment frequencies in their peripheral blood, whereas totally mismatched sibs were, in general, the most dissimilar; HLA haploidentical sibs tended to be intermediate between the two groups. The degree of similarity among HLA-identical sibs was comparable to that observed among three pairs of identical twins suggesting that HLA is the major genetic component influencing TCR V-segment frequency. Consistent with this observation, it was found that the frequency of T cells expressing particular V beta segments was skewed towards either CD4+ or CD8+ cells indicating that T cells expressing some V beta genes may be positively selected primarily by class I or class II major histocompatibility complex proteins. Finally, it was observed that individuals who express the HLA class I specificity, B38, tend to express high levels of V alpha 2.3+ cells among their CD8+ T cells. These observations represent definitive proof that human V-segment frequencies are profoundly influenced by the HLA complex.

T Cells: A Growing Universe of Roles in Neurodegenerative Diseases

2021 ◽  
pp. 107385842110249
Author(s):  
Dallin Dressman ◽  
Wassim Elyaman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Neurodegenerative Diseases ◽  
Human Leukocyte ◽  
Autoimmune Response ◽  
Antigen Specificity ◽  
Risk Genes ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
The Central Nervous System

T cells play a central role in homeostasis and host defense against infectious diseases. T cell dysregulation can lead to recognizing self-antigens as foreign antigens, causing a detrimental autoimmune response. T cell involvement in multiple sclerosis (MS), long understood to be an autoimmune-mediated neurodegenerative disease, is well characterized. More recently, a role for T cells has also been identified for the neurodegenerative diseases Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Interestingly, several alleles and variants of human leukocyte antigen (HLA) genes have been classified as AD and PD risk genes. HLA codes for components of major histocompatibility complex (MHC) class I or class II, both of which are expressed by microglia, the innate immune cells of the central nervous system (CNS). Thus, both microglia and T cells may potentially interact in an antigen-dependent or independent fashion to shape the inflammatory cascade occurring in neurodegenerative diseases. Dissecting the antigen specificity of T cells may lead to new options for disease-modifying treatments in neurodegenerative diseases. Here, we review the current understanding of T cells in neurodegenerative diseases. We summarize the subsets of T cells, their phenotype and potential functions in animal models and in human studies of neurodegenerative diseases.

scholarly journals Recent advances in T-cell engineering for use in immunotherapy

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2344 ◽  
Author(s):  
Preeti Sharma ◽  
David M. Kranz
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Complex Molecule ◽  
Major Histocompatibility Complex Molecule ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Single Chain ◽  
Cell Therapies ◽  
Recent Advances

Adoptive T-cell therapies have shown exceptional promise in the treatment of cancer, especially B-cell malignancies. Two distinct strategies have been used to redirect the activity of ex vivo engineered T cells. In one case, the well-known ability of the T-cell receptor (TCR) to recognize a specific peptide bound to a major histocompatibility complex molecule has been exploited by introducing a TCR against a cancer-associated peptide/human leukocyte antigen complex. In the other strategy, synthetic constructs called chimeric antigen receptors (CARs) that contain antibody variable domains (single-chain fragments variable) and signaling domains have been introduced into T cells. Whereas many reviews have described these two approaches, this review focuses on a few recent advances of significant interest. The early success of CARs has been followed by questions about optimal configurations of these synthetic constructs, especially for efficacy against solid tumors. Among the many features that are important, the dimensions and stoichiometries of CAR/antigen complexes at the synapse have recently begun to be appreciated. In TCR-mediated approaches, recent evidence that mutated peptides (neoantigens) serve as targets for endogenous T-cell responses suggests that these neoantigens may also provide new opportunities for adoptive T-cell therapies with TCRs.

scholarly journals Biased T Cell Receptor Usage Directed against Human Leukocyte Antigen DQ8-Restricted Gliadin Peptides Is Associated with Celiac Disease

Immunity ◽  
2012 ◽  
Vol 37 (4) ◽  
pp. 611-621 ◽  
Author(s):  
Sophie E. Broughton ◽  
Jan Petersen ◽  
Alex Theodossis ◽  
Stephen W. Scally ◽  
Khai Lee Loh ◽  
...  
Keyword(s):  
Celiac Disease ◽  
T Cell ◽  
Human Leukocyte Antigen ◽  
T Cell Receptor ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Leukocyte Antigen ◽  
Receptor Usage ◽  
Gliadin Peptides

scholarly journals Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2227-2236 ◽  
Author(s):  
NA Kernan ◽  
C Bordignon ◽  
G Heller ◽  
I Cunningham ◽  
H Castro-Malaspina ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cells ◽  
T Cell ◽  
Human Leukocyte Antigen ◽  
Graft Failure ◽  
Human Leukocyte ◽  
Marrow Transplant ◽  
High Dose ◽  
Leukocyte Antigen ◽  
Major Factors

Abstract Risk factors for graft failure were analyzed in 122 recipients of an allogeneic T-cell-depleted human leukocyte antigen (HLA)-identical sibling marrow transplant as treatment for leukemia. In each case pretransplant immunosuppression included 1,375 to 1,500 cGy hyperfractionated total body irradiation and cyclophosphamide (60 mg/kg/d x 2). No patient received immunosuppression prosttransplant for graft-versus-host disease (GVHD) prophylaxis. Nineteen patients in this group experienced graft failure. The major factors associated with graft failure were transplants from male donors and the age of the patient (or donor). Among male recipients of male donor-derived grafts a low dose per kilogram of nucleated cells, progenitor cells (colony forming unit-GM) and T cells was also associated with graft failure. Additional irradiation to 1,500 cGy, high dose corticosteroids posttransplant, and additional peripheral blood donor T cells did not decrease the incidence of graft failure. In addition, type of leukemia, time from diagnosis to transplant, an intact spleen, or the presence of antidonor leukocyte antibodies did not correlate with graft failure. To ensure engraftment of secondary transplants, further immunosuppression was necessary but was poorly tolerated. However, engraftment and survival could be achieved with an immunosuppressive regimen in which antithymocyte globulin and high dose methylprednisolone were administered both before and after infusions of secondary partially T- cell-depleted marrow grafts.

Defective T Cell Migration in Chronic Lymphocytic Leukemia Is Repaired by Lenalidomide

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3117-3117
Author(s):  
Alan G. Ramsay ◽  
Lena Svensson ◽  
Nancy Hogg ◽  
John G. Gribben
Keyword(s):  
T Cells ◽  
Cell Migration ◽  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Cd8 T Cells ◽  
Direct Contact ◽  
Immune Surveillance ◽  
Lymphocytic Leukemia ◽  
T Cell Migration

Abstract We have previously demonstrated that multiple gene expression abnormalities are induced in T cells from chronic lymphocytic leukemia (CLL) patients including defects within the actin cytoskeleton signaling pathways that control immune recognition and motility (Gullu et al. JCI, 2005). T cell immune surveillance requires rapid migratory responses and LFA-1 (CD11a/CD18; αLβ2) is a promigratory receptor that engages the cytoskeleton to control migration. We hypothesized that CLL T cells may exhibit dysfunctional migration in response to ICAM-1, the principal ligand for LFA-1. Using time lapse microscopy, we observed significantly reduced chemokine SDF-1 (CXCL12) induced migration on ICAM-1 of CLL CD4 and CD8 T cells compared to age-matched healthy donor T cells. Healthy T cells tracked for 45 min displayed a random course of migration with an average speed of ~ 8 μm/min, whereas CLL T cells were slower ~ 5 μm/min (n=14, ~ 30% reduction, p<0.01). We further postulated that direct contact of CLL tumor cells with healthy T cells would induce this migratory defect. Healthy CD4 or CD8 T cells were cocultured with either allogeneic CLL B cells or allogeneic healthy B cells and subsequently used in migration assays. Co-culture with CLL cells resulted in significantly reduced T cell migration compared with co-culture with healthy B cells (~ 44% reduction in migration, n=6, p<0.01). Evidence that direct contact was required to induce this migratory defect was shown when no effect was observed when cell-cell adhesion was prevented by pretreatment of CLL cells with anti-ICAM-1 blocking antibody prior to primary co-culture with healthy T cells. This cancer-induced migratory defect was repaired when CLL T cells were pretreated with the immunomodulatory drug Lenalidomide (1μM for 1hr). Treatment with this agent enhanced the migratory potential of CLL T cells to a speed comparable to untreated and treated healthy T cells. The finding that lenalidomide can restore rapid migration in patient T cells provides evidence that this agent may increase immune surveillance in CLL patients.

scholarly journals Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 788-797 ◽  
Author(s):  
Aaron P. Rapoport ◽  
Nicole A. Aqui ◽  
Edward A. Stadtmauer ◽  
Dan T. Vogl ◽  
Hong-Bin Fang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Leukocyte Antigen ◽  
Conjugate Vaccine ◽  
Tumor Antigen ◽  
Pneumococcal Conjugate Vaccine ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Cell Counts ◽  
Antigen Vaccine

AbstractIn a phase 1/2 two-arm trial, 54 patients with myeloma received autografts followed by ex vivo anti-CD3/anti-CD28 costimulated autologous T cells at day 2 after transplantation. Study patients positive for human leukocyte antigen A2 (arm A, n = 28) also received pneumococcal conjugate vaccine immunizations before and after transplantation and a multipeptide tumor antigen vaccine derived from the human telomerase reverse transcriptase and the antiapoptotic protein survivin. Patients negative for human leukocyte antigen A2 (arm B, n = 26) received the pneumococcal conjugate vaccine only. Patients exhibited robust T-cell recoveries by day 14 with supraphysiologic T-cell counts accompanied by a sustained reduction in regulatory T cells. The median event-free survival (EFS) for all patients is 20 months (95% confidence interval, 14.6-24.7 months); the projected 3-year overall survival is 83%. A subset of patients in arm A (36%) developed immune responses to the tumor antigen vaccine by tetramer assays, but this cohort did not exhibit better EFS. Higher posttransplantation CD4+ T-cell counts and a lower percentage of FOXP3+ T cells were associated with improved EFS. Patients exhibited accelerated polyclonal immunoglobulin recovery compared with patients without T-cell transfers. Adoptive transfer of tumor antigen vaccine-primed and costimulated T cells leads to augmented and accelerated cellular and humoral immune reconstitution, including antitumor immunity, after autologous stem cell transplantation for myeloma. This study was registered at www.clinicaltrials.gov as NCT00499577.

Sign in / Sign up

Export Citation Format

Share Document