scholarly journals Intercellular interactions and cytokine responsiveness of peritoneal alpha/beta and gamma/delta T cells from Listeria-infected mice: synergistic effects of interleukin 1 and 7 on gamma/delta T cells.

1993 ◽  
Vol 178 (3) ◽  
pp. 985-996 ◽  
Author(s):  
M J Skeen ◽  
H K Ziegler
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
T Cell Subsets ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Accessory Cells ◽  
Alpha Beta ◽  
Gamma Delta T Cell

Peritoneal gamma/delta T cells from Listeria-immune mice show an enhanced potential to expand when restimulated with antigens or mitogens in vitro (see companion paper [Skeen, M. J., and H. K. Ziegler. 1993. J. Exp. Med. 178:971]). When cocultured with peritoneal alpha/beta T cells, the gamma/delta T cell population expanded preferentially even when the in vitro stimulus was specific for the alpha/beta T cell population. Purified gamma/delta T cells did not respond to alpha/beta T cell-specific stimuli. If isolated T cell subsets were recombined in cell mixing experiments, the resulting proliferative response was greater than additive. Irradiated alpha/beta T cells could enhance the proliferation of responding gamma/delta T cells, but the effect was unidirectional; i.e., irradiated gamma/delta T cells did not stimulate responding gamma/delta T cells. This effect appeared to be cytokine mediated and did not require cell-cell contact. Both recombinant interleukin 2 (rIL-2) and rIL-7 could support the expansion of the gamma/delta T cells, while rIL-7 was only minimally stimulatory for the alpha/beta T cells. The magnitude of the response by gamma/delta T cells to rIL-7 exceeded the response to other in vitro stimuli, including immobilized anti-T cell receptor monoclonal antibody, and was 50-100-fold greater than the alpha/beta T cell response to IL-7. This unique sensitivity of gamma/delta T cells to IL-7 was strongly enhanced by the presence of accessory cells. These cells could be replaced by rIL-1, establishing a synergy for IL-1 and IL-7 as factors that could uniquely stimulate this gamma/delta T cell population. Isolated peritoneal gamma/delta T cells from Listeria-immune mice react to heat-killed Listeria preparations in the presence of macrophages accessory cells in a non-H-2-restricted manner. Considered collectively, these results suggest a potential mechanism by which gamma/delta T cells can predominate in epithelial tissues and at sites of infection.

scholarly journals Induction of murine peritoneal gamma/delta T cells and their role in resistance to bacterial infection.

1993 ◽  
Vol 178 (3) ◽  
pp. 971-984 ◽  
Author(s):  
M J Skeen ◽  
H K Ziegler
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peritoneal Cavity ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Gram Positive ◽  
Gram Negative ◽  
A Site ◽  
Gamma Delta T Cell

Previous studies have reported an association of gamma/delta T cells with microbial infection in both human lesions and murine infectious disease models. In this study we provide a comprehensive analysis of the conditions under which the induction of gamma/delta T cells occurs at a site of infection. We found a site-specific induction of gamma/delta T cells after the injection of Listeria monocytogenes in the peritoneal cavity of C3H mice. No changes were seen in the splenic or lymph node populations after these injections. Both the proportion and the absolute number of gamma/delta T cells increased in the peritoneal cavity. Additionally, when peritoneal T cells from Listeria-immune mice were restimulated in vitro, the induced gamma/delta T cells exhibited a greater expansion potential than the alpha/beta T cells. Neither the induced gamma/delta T cells nor those from normal mice expressed CD4 or CD8 on the cell surface. Thy-1 was expressed on only 29% of normal peritoneal gamma/delta T cells, but after intraperitoneal Listeria injection 65% of induced gamma/delta T cells expressed. Thy-1, Pgp-1 and CD45R expression on both normal and induced gamma/delta T cells was consistent with an activation phenotype. Significant increases in peritoneal gamma/delta T cells were not seen until 5-7 d after Listeria injection. The proportion of the CD3+ population expressing the gamma/delta T cell receptor remained elevated for 6-7 wk, while the absolute numbers of peritoneal gamma/delta T cells declined gradually over this time period, reflecting a decrease in both the number of lymphocytes and the percentage of these that were CD3+. Peak numbers of gamma/delta T cells were seen at day 10 with live microbes such as Listeria. A variety of microbes, toxins, mitogens, antigens, cytokines, and nonspecific inflammatory agents were evaluated for their ability to induce gamma/delta T cells in the peritoneal cavity. Both Gram-positive and Gram-negative bacteria as well as Mycobacteria were able to induce gamma/delta T cells that showed increased in vitro expansion potential. An exotoxin from a Gram-positive organism, listeriolysin-o, and the lipopolysaccharide (LPS) endotoxin from a Gram-negative organism were also effective. gamma/delta T cell responses to LPS were under lps gene control. Peak numbers of gamma/delta T cells were observed at day 3 after injection with exotoxins and endotoxins. Modifications that abrogated the virulence of a bacterial strain also eliminated the inductive effect for gamma/delta T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Retroviral transformation in vitro of chicken T cells expressing either alpha/beta or gamma/delta T cell receptors by reticuloendotheliosis virus strain T.

1993 ◽  
Vol 177 (3) ◽  
pp. 647-656 ◽  
Author(s):  
M D Marmor ◽  
T Benatar ◽  
M J Ratcliffe
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Reticuloendotheliosis Virus ◽  
Spleen Cells ◽  
Gamma Delta ◽  
Alpha Beta ◽  
Gamma Delta T Cell

Exposure of normal juvenile chicken bone marrow cells to the replication defective avian reticuloendotheliosis virus strain T (REV-T) (chicken syncytial virus [CSV]) in vitro resulted in the generation of transformed cell lines containing T cells. The transformed T cells derived from bone marrow included cells expressing either alpha/beta or gamma/delta T cell receptors (TCRs) in proportions roughly equivalent to the proportions of TCR-alpha/beta and TCR-gamma/delta T cells found in the normal bone marrow in vivo. Essentially all TCR-alpha/beta-expressing transformed bone marrow-derived T cells expressed CD8, whereas few, if any, expressed CD4. In contrast, among TCR-gamma/delta T cells, both CD8+ and CD8- cells were derived, all of which were CD4-. Exposure of ex vivo spleen cells to REV-T(CSV) yielded transformed polyclonal cell lines containing > 99% B cells. However, REV-T(CSV) infection of mitogen-activated spleen cells in vitro resulted in transformed populations containing predominantly T cells. This may be explained at least in part by in vitro activation resulting in dramatically increased levels of T cell REV-T(CSV) receptor expression. In contrast to REV-T(CSV)-transformed lines derived from normal bone marrow, transformed lines derived from activated spleen cells contained substantial numbers of CD4+ cells, all of which expressed TCR-alpha/beta. While transformed T cells derived from bone marrow were stable for extended periods of in vitro culture and were cloned from single cells, transformed T cells from activated spleen were not stable and could not be cloned. We have therefore dissociated the initial transformation of T cells with REV-T(CSV) from the requirements for long-term growth. These results provide the first demonstration of efficient in vitro transformation of chicken T lineage cells by REV-T(CSV). Since productive infection with REV-T(CSV) is not sufficient to promote long-term growth of transformed cells, these results further suggest that immortalization depends not only upon expression of the v-rel oncogene but also on intracellular factor(s) whose expression varies according to the state of T cell physiology and/or activation.

scholarly journals Double-Negative T-Cell Reaction in a Case of Listeria Meningitis

2021 ◽  
Vol 18 (12) ◽  
pp. 6486
Author(s):  
Asad Ullah ◽  
G. Taylor Patterson ◽  
Samantha N. Mattox ◽  
Thomas Cotter ◽  
Nikhil G. Patel ◽  
...  
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
T Cell ◽  
Cell Population ◽  
Cerebral Spinal Fluid ◽  
Spinal Fluid ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Listeria Meningitis ◽  
Gamma Delta T Cell

Gamma delta T-cells are commonly found in response to Listeria monocytogenes infection in mice, whereas this same immunological response has only been reported a few times in vivo in humans. Moreover, gamma delta T-cell response in cerebral spinal fluid samples in conjunction with Listeria meningitis has never been described in medical literature to date. Thus, we describe a 64-year-old male who presented with altered mental status, fever, and neck stiffness. After lumbar puncture revealed elevated glucose, protein, lactate dehydrogenase, and white blood cell count, further cytologic analysis was indicated. The CSF showed a markedly hypercellular sample with a lymphocytic pleocytosis, including some enlarged forms with irregular nuclear contours, and rare macrophage containing intracytoplasmic bacteria. Lymphocyte immunophenotyping was performed via flow cytometric analysis, which ultimately revealed a prominent CD4/CD8 negative T-cell population, suggestive of a gamma delta T-cell population. Thus, an initial suspicion of malignancy was considered but was ruled out due to the absence of mass lesion on imaging and overall features including heterogenous lymphocyte morphology. Shortly after, gram stain and cultures were obtained revealing Listeria monocytogenes. Unfortunately, the patient rapidly succumbed to disease following the diagnosis of Listeria meningitis. Studies suggest that gamma delta T-cells are activated by the protein components of Listeria and thus have been found to be an important mediator of resistance to Listeria infection. Studies have also discovered that the level of activation for these T-cells appears to be tissue specific and dose dependent, with most cases occurring within visceral organs. Hence, we herein present the first case of gamma delta T-cell activation due to Listeria monocytogenes within the cerebral spinal fluid of a human patient.

Improved Overall Survival in Patients Recovering with High Gamma/Delta T Cells after Allogeneic Haematopoietic Stem Cell Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2223-2223
Author(s):  
Lambros Kordelas ◽  
Matthias Junge ◽  
Rudolf Trenschel ◽  
Ahmet H Elmaagacli ◽  
Dietrich W Beelen
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
T Cell ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Cell Recovery ◽  
Cell Numbers ◽  
High Gamma ◽  
Alpha Beta ◽  
Gamma Delta T Cell

Abstract T-cells play a crucial role in the Graft-versus-Leukemia (GvL)-effect, since T-cells depleted grafts are associated with a higher relapse risk. Unfortunately, the GvL-effect is often associated with Graft-versus-Host-Disease (GvHD). T-cells can be divided into two phenotypic sub-groups by the expression of specific alpha/beta- and gamma/delta T-cell receptors. Gamma/delta-T-cells might provide a useful source for T-cell-immunotherapy since they may exert a GvL-effect without inducing a GvHD-risk. Only few studies have been carried out investigating the possible impact of gamma/delta-T-cell recovery following allogeneic hematopoietic stem cell transplantation (HSCT). A recent prospective study (Godder et al., BMT 2007) indicates a survival advantage for patients (pts) recovering with higher gamma/delta-T-cell numbers following HSCT. The data presented here emerge from a single-centre analysis evaluating the possible impact of higher gamma/delta-T-cell numbers following HSCT in pts with hematologic malignancies. We included all patients who had at least three consecutive analyses of alpha/beta- and gamma/delta-T-cell numbers within the first year after HSCT. This cohort of 107 patients includes the following haematological malignancies: AML (n=40), CML (n=19), ALL (n=13), MDS (n=11), OMF (n=9), NHL (n=7), and other diseases (n=8). Median patient age was 41 years (range 16 – 67 years). Median donor age was 38 years (range 18 – 70 years). HSCT was performed with related donors in 37 pts (35%) and with unrelated donors in 70 pts (65%). We defined the threshold for “high” gamma/delta-T-cell recovery as three ore more absolute gamma/delta-T-cell numbers above the absolute median gamma/delta-T number in the peripheral blood within the first 12 months after HSCT. According to this threshold 29 pts (27%) recovered with “high” gamma/delta-T-cells. These pts achieved a significantly higher overall survival with lower gamma/delta-T-cell numbers (log-rank p .029). This resulted from a lower relapse risk and a lower risk for acute GvHD. In multivariate analysis including other prognostic factors of overall survival (patient age, disease status, donor type, grades of acute GvHD and relapse), the beneficial effect of “high” gamma/delta-T-cell recovery could be confirmed. In contrast, recovery of alpha/beta T-cell numbers in peripheral blood had no significant influence on HSCT endpoints and were further not associated with the recovery of gamma/delta T-cells. This analysis supports the hypothesis of a beneficial effect of high gamma/delta-T-cells recovery following HSCT regarding overall survival. Further analyses and research are warranted to determine more accurately the importance of increased recovery of gamma/delta-T-cells to possibly develop new therapeutic options in HSCT as e.g. graft engineering.

scholarly journals Small nucleolar RNAs are concomitantly down-regulated during murine gamma delta T-cell development.

2019 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
T Cell Development ◽  
Cell Development ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Cell Receptors ◽  
Alpha Beta ◽  
Gamma Delta T Cell

Gamma delta T-cells are a lymphocyte subset that display gamma delta T-cell receptors rather than the alpha beta T-cell receptors that alpha beta T cells like CD4 helper and CD8 cytotoxic T-cells display, and whose function straddles the intersection of innate and adaptive immune cells (1). To understand the transcriptional behavior of gamma delta T-cells during mammalian development, we performed global differential gene expression of datasets encompassing transcriptome data from embryonic and adult gamma delta T-cells from mice (2). These analyses revealed a species of non-coding RNA termed small nucleolar RNA, or snoRNA were among the most differentially expressed genes when comparing embryonic and adult gamma delta T-cells. Moreover, these snoRNA were uniformly down-regulated over the course of gamma delta T-cell development. These data demonstrate unprecedented developmental repression of snoRNA in lymphocytes and suggest that stage-specific repression of snoRNAs may serve some vital developmental purpose in the function of gamma delta T-cells.

101 Engineering gamma/delta T cells with the T-Cell antigen coupler receptor effectively induces antigen-specific tumor cytotoxicity in vitro and in vivo

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A112-A112
Author(s):  
Sarah Asbury ◽  
Seung Mi Yoo ◽  
Jonathan Bramson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Cell Therapies ◽  
Alpha Beta ◽  
Tumor Cytotoxicity ◽  
Gamma Delta T Cell ◽  
Anti Tumor Activity

BackgroundEngineered T cell therapies have revolutionized treatment of relapsed refractory haematological malignancies, however the cost of treatment for autologous products remains a significant challenge to their widespread use. The high cost is driven largely by the need for personalized manufacturing of autologous cell products. A non-conventional class of T cells, the gamma/delta T cell, can be safely transplanted into an unrelated recipient without inducing graft-versus host disease,1 making them an ideal candidate for mass-manufactured off-the-shelf T cell therapies. We have previously described a novel method of directing conventional alpha/beta T cells towards tumour targets by co-opting the T cell receptor using the T cell Antigen Coupler (TAC) receptor.2 Here, we describe the use of TAC receptors to engineer antigen-specific reactivity into gamma/delta T cells, resulting in highly potent anti-tumor cytotoxicity.MethodsEngineered gamma/delta T cells were manufactured by activating PBMCs with Zoledronate and IL-2. The TAC transgene was introduced into T cells using either VSV-G pseudotype lentivirus or GALV-psuedotyped gamma-retrovirus vectors.Through optimization studies, we determined transduction was highest 24 hours post-activation for lentivirus and 72 hours post-activation for gamma-retrovirus. Cultures were fed with IL-2 supplemented media every 2 – 3 days and enriched on Day 14 to >99% gamma/delta T cell purity using CD4/CD8 magnetic-activated cell sorting depletion (Miltenyi Biotec).ResultsBoth methods of gene transfer tested for our pilot study yielded excellent gene transduction (40% - 70%). Using lentivirus-engineered gamma/delta T cells, we demonstrated that the TAC receptor re-directs gamma/delta T cells to attack tumors in an antigen-specific manner. The presence of the TAC receptor did not interfere with lysis of tumor cells via the natural tumor-reactive gamma/delta T cell receptors. Importantly, TAC-engineered gamma/delta T cells displayed robust cytotoxicity at very low effector:target ratios (<1) and caused regression of human tumor xenografts that were otherwise resistant to non-engineered gamma/delta T cells. Curiously, gamma/delta T cell manufacturing was sensitive to the quality of the lentivirus product, where products with low titers were associated with outgrowth of conventional alpha/beta T cells. Outgrowth of alpha/beta T cells was not observed with gamma-retroviruses. We are presently evaluating the anti-tumor activity of gamma-retrovirus-engineered gamma/delta T cells.ConclusionsOff-the-shelf engineered gamma/delta T cells represent a strategy to reduce manufacturing cost and may represent the next generation of engineered T cell therapies.TAC receptors provide a robust tool for directing gamma/delta T cells to attack tumors that are otherwise resistant to gamma/delta T cells and should be evaluated further.AcknowledgementsThis work was supported by the Samuel Family Foundation, the Ontario Centres of Excellence and Triumvira Immunologics.Ethics ApprovalThe study was approved by McMaster’s Animal Research Ethics Board, AUP#19-02-10.ReferencesArruda LCM, Gaballa A, Uhlin M. Impact of γδ T cells on clinical outcome of hematopoietic stem cell transplantation: systematic review and meta-analysis. Blood Adv 2019;3(21):3436–3448.Helsen CW, Hammill JA, Lau VWC, et al. The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity. Nat Commun 2018;9(1):3049.

Rapamycin Together With TGF-β1, IL-2 and IL-15 Induces The Generation Of Functional Regulatory γδT Cells From Human Peripheral Blood Mononuclear Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3482-3482
Author(s):  
Yanjun Gu ◽  
Yongxian Hu ◽  
Kaimin Hu ◽  
Weichao Liao ◽  
Feilin Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Human Immune System ◽  
Gamma Delta T Cell ◽  
Tgf Β1

Abstract Gamma delta T cell, expressing gamma delta T cell receptor (gamma delta TCR), is considered as a group of unconventional T cells linking innate and adaptive immunity. Although gamma delta T cells only represent a minor population in human immune system, their functions are very broad. Recent researches have suggested that depending on the microenvironment, gamma delta T cells can assume features reminiscent of Th1, Th2, Th17 and regulatory T cells (Treg) as well as professional antigen present cells. Regulatory gamma delta T cell (gamma delta Treg) is a recently reported subset of gamma delta T cells characterized by both expressions of gamma delta TCR and forkhead/winged-helix family transcriptional repressor p3 (Foxp3), with potential immunosuppressive functions. Researches that focused on gamma delta Treg have showed the regulatory roles it has in preventing autoimmune response and relieving autoimmune diseases such as systemic lupus erythematosus (SLE), and the suppressive activity of breast tumor-derived gamma delta Tregs on innate and adaptive immunity, as well as the protective effects enhanced by gamma delta Tregs against xenogenic graft-versus-host disease in humanized mice found in our previous studies. All these observations suggest the important roles that gamma delta Treg plays in human immune system and its potential clinical applications. However, the further studies of gamma delta Treg are limited mainly due to its low quantities in vivo and the lack of methods to induce gamma delta Treg largely in vitro. It would be much significant if we found efficient induction and expansion methods for functional gamma delta Tregs. As the mammalian target of rapamycin (mTOR) is an important integrative kinase that acts as a crucial negative regulator of Treg differentiation and expansion, which can inhibit the expression of Foxp3 induced by TGF-β1, and Rapamycin (Rapa) is an immunosuppressive agent which acts through the blockade of mTOR, here we studied whether Rapa, together with TGF-β1/IL-2/IL-15, could induce and expand gamma delta Tregs derived from human peripheral blood mononuclear cells (hPBMCs) efficiently in vitro, under the stimulation of zoledronic acid (ZOL). Our results demonstrated that Rapa, synergized with TGF-β1/IL-2/IL-15, could not only facilitate the generation of gamma delta Tregs largely in vitro, with the percentage of induced gamma delta Tregs increasing from 2.4±1.2% cultured without TGF-β1/IL-15 nor Rapa, to 55.2±8.2% with Rapa and TGF-β1/IL-2/IL-15 together, compared with 26.2±6.7% with TGF-β1/IL-2/IL-15 but no Rapa (as Figure 1A indicated), but also enhanced the Foxp3 and CD25 expression levels in Rapa-induced gamma delta Tregs (as Figure 1C). Other regulatory-associated molecules expressed in Rapa-induced gamma delta Tregs included CTLA-4, ICOS and HLA-DR, and approximately no CD127, which were somehow similar with conventional CD4+CD25+ Tregs and were related with strong immunosuppressive functions. Through the co-culturing with naïve T cells derived from hPBMCs in vitro, we found that thus-induced gamma delta Tregs displayed concentration-dependent suppressive activity against the proliferation of naïve T cells, and this suppressive function appeared much greater in Rapa-induced gamma delta Tregs, compared with those induced without Rapa (as Figure 1B indicated).Figure 1Figure 1. In conclusion, our results demonstrated that Rapa, combined with TGF-β1/IL-2/IL-15, could induce and expand gamma delta Tregs largely in vitro and thus-induced gamma delta Tregs expressed high levels of Foxp3 and CD25, and displayed significant immunosuppressive activities in vitro, which provided bases to some extent for the further studies on gamma delta Treg and its potential clinical applications. Disclosures: No relevant conflicts of interest to declare.

600 In vitro anticancer and immunomodulatory activities of NBT-167, a dimer of resveratrol

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A635-A635
Author(s):  
Jeffrey Zhang ◽  
Everett Henry ◽  
L Harris Zhang ◽  
Wanying Zhang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Immune Cells ◽  
Cell Killing ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Raw264.7 Macrophages

BackgroundResveratrol (3,4’,5-trihydroxystilbene), a stilbenoid isolated from many species of plants, is widely known for its antioxidative, anti-inflammatory, immunomodulatory and anticancer activities. Recently, novel resveratrol oligomers have been isolated from various plants; their diverse structures are characterized by the polymerization of two or more resveratrol units. Little is known regarding the anticancer and immunomodulating activities of these oligomers. In this study, we designed in vitro models to compare resveratrol side by side with its natural dimer NBT-167 for their anticancer and immunological activities.MethodsWe isolated resveratrol and its dimer (NBT-167) from plants. The potency of the compounds was compared side by side using cancer cell survival assays and immunological assays with various types of human cells including cancer cell lines, PBMCs and enriched NK, gamma delta T cells, THP-1 monocytic cells, HL-60 promyelocytic leukemia cells as well as mouse RAW264.7 macrophages.ResultsNBT-167 was found to be more potent than resveratrol in inhibiting growth of various cancer cells and modulation of cytokine production from anti-IgM, LPS, PHA or SEB stimulated PBMC. Both compounds similarly enhanced IL-2 stimulated NK and gamma delta T cell killing activity against K562 cells and modulated nitric oxide production from LPS/IFN-g induced RAW264.7 macrophages and phagocytotic activity of HL-60 cells. NBT-167 was slightly more potently than resveratrol in inhibiting chemotaxis of HL-60 cells and blocking cell cycle of THP-1 and HL-60 cells at G1/S transition. In addition, NBT-167, but not resveratrol, could increase IL-2 production and T cell proliferation stimulated with anti-CD3 and anti-CD28 and synergize with anti-PD-1 antibody to increase IL-2 and IFN-gamma production in co-culture of allotypic T cells and dendric cells (MLR).ConclusionsOur data showed that NBT-167, a dimer of resveratrol, had anticancer and immunomodulatory activities such as modulation of expression of cytokines in immune cells and induction of cancer cell-killing activities of NK and gamma delta T cells. Generally, NBT-167 appeared to have higher activities than resveratrol in modulating immune cells and inhibiting cancer cells. NBT-167 could be a promising cancer immunotherapeutic agent targeting both cancer cells and immune cells.

scholarly journals Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells.

1996 ◽  
Vol 183 (5) ◽  
pp. 2271-2282 ◽  
Author(s):  
L Wen ◽  
W Pao ◽  
F S Wong ◽  
Q Peng ◽  
J Craft ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Autoantibody Production ◽  
Ige Synthesis ◽  
Alpha Beta ◽  
T Cell Help

The production of class-switched antibodies, particularly immunoglobulin (Ig) G1 and IgE, occurs efficiently in T cell receptor (TCR) alpha-/- mice that are congenitally devoid of alpha/beta T cells. This finding runs counter to a wealth of data indicating that IgG1 and IgE synthesis are largely dependent on the collaboration between B and alpha/beta T cells. Furthermore, many of the antibodies synthesized in TCR alpha-/- mice are reactive to a similar spectrum of self-antigens as that targeted by autoantibodies characterizing human systemic lupus erythematosus (SLE). SLE, too, is most commonly regarded as an alpha/beta T cell-mediated condition. To distinguish whether the development of autoantibodies in TCR alpha-/- mice is due to an intrinsic de-regulation of B cells, or to a heretofore poorly characterized collaboration between B and "non-alpha/beta T" cells, the phenotype has been reconstituted by transfer of various populations of B and non-alpha/beta T cells including cloned gamma/delta T cells derived from TCR alpha-/- mice, to severe combined immunodeficient (SCID) mice. The results establish that the reproducible production of IgG1 (including autoantibodies) is a product of non-alpha/beta T cell help that can be provided by gamma/delta T cells. This type of B-T collaboration sustains the production of germinal centers, lymphoid follicles that ordinarily are anatomical signatures of alpha/beta T-B cell collaboration. Thus, non-alpha/beta T cell help may drive Ig synthesis and autoreactivity under various circumstances, especially in cases of alpha/beta T cell immunodeficiency.

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