scholarly journals In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3- 4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 844-850 ◽  
Author(s):  
RP Witherspoon ◽  
LG Lum ◽  
R Storb ◽  
ED Thomas
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Hematologic Malignancy ◽  
Plaque Assay ◽  
Pokeweed Mitogen ◽  
Lymphocyte Function ◽  
Peripheral Blood Mononuclear ◽  
Immunoglobulin Secretion

Abstract Immunoglobulin secretion was studied in 37 patients between 19 and 106 days after allogeneic HLA-identical (30 patients), allogeneic one HLA- haplotype-identical (three patients), syngeneic (three patients), or autologous (one patient) marrow grafting. E rosette-positive (T) and E rosette-negative (non-T) peripheral blood mononuclear cells were cocultured with pokeweed mitogen for 6 days. Polyvalent immunoglobulin secretion was determined by counting plaque forming cells in a reverse hemolytic plaque assay. The number of antibody secreting cells in cocultures of autologous T and non-T lymphocytes was low in 40 of 44 tests conducted on samples from the 37 patients. Mononuclear or non-T cells from 38 of 40 tests failed to produce antibody when cultured with normal helper T cells. T cells from 23 of 37 tests failed to help normal non-T cells secrete antibody. T lymphocytes from 23 of 41 tests suppressed antibody production greater than 80% by normal T and non-T cells. The suppressor cells were radiosensitive in 17 of the 25 tests. The abnormal function of lymphocyte subpopulations in patients during the first 3 mo after syngeneic, allogeneic or autologous marrow grafting was similar regardless of the type of graft or the presence of acute graft versus host disease.

scholarly journals In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3- 4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 844-850 ◽  
Author(s):  
RP Witherspoon ◽  
LG Lum ◽  
R Storb ◽  
ED Thomas
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Hematologic Malignancy ◽  
Plaque Assay ◽  
Pokeweed Mitogen ◽  
Lymphocyte Function ◽  
Peripheral Blood Mononuclear ◽  
Immunoglobulin Secretion

Immunoglobulin secretion was studied in 37 patients between 19 and 106 days after allogeneic HLA-identical (30 patients), allogeneic one HLA- haplotype-identical (three patients), syngeneic (three patients), or autologous (one patient) marrow grafting. E rosette-positive (T) and E rosette-negative (non-T) peripheral blood mononuclear cells were cocultured with pokeweed mitogen for 6 days. Polyvalent immunoglobulin secretion was determined by counting plaque forming cells in a reverse hemolytic plaque assay. The number of antibody secreting cells in cocultures of autologous T and non-T lymphocytes was low in 40 of 44 tests conducted on samples from the 37 patients. Mononuclear or non-T cells from 38 of 40 tests failed to produce antibody when cultured with normal helper T cells. T cells from 23 of 37 tests failed to help normal non-T cells secrete antibody. T lymphocytes from 23 of 41 tests suppressed antibody production greater than 80% by normal T and non-T cells. The suppressor cells were radiosensitive in 17 of the 25 tests. The abnormal function of lymphocyte subpopulations in patients during the first 3 mo after syngeneic, allogeneic or autologous marrow grafting was similar regardless of the type of graft or the presence of acute graft versus host disease.

Spontaneous in vitro immunoglobulin secretion at the diagnosis of insulin-dependent diabetes

1984 ◽  
Vol 105 (4) ◽  
pp. 521-527 ◽  
Author(s):  
Geroge Papadopoulos ◽  
Jørgen Petersen ◽  
Vagn Andersen ◽  
Åke Lernmark ◽  
Birgitte Marner ◽  
...  
Keyword(s):  
Islet Cell ◽  
Mononuclear Cells ◽  
Plaque Assay ◽  
Islet Cell Antibodies ◽  
Pokeweed Mitogen ◽  
C Peptide ◽  
Immunoglobulin Secretion ◽  
Insulin Dependent ◽  
Spontaneous Secretion

Abstract. Blood mononuclear cells obtained from 17 newly diagnosed insulin-dependent diabetic (IDDM) patients treated with insulin for 5 –7 days were assessed for the number of spontaneous and pokeweed mitogen (PWM)-stimulated immunoglobulin-secreting cells in a reverse haemolytic plaque assay. The spontaneous in vitro immunoglobulin secretion was evanescent and decreased in individual patients within 1–4 months of insulin treatment. Compared to matched controls, 53% (9/17) of the IDDM patients had an elevated spontaneous secretion of immunoglobulin, 41% (7/17) for IgG, 35% (6/17) for IgM, and 35% (6/17) for IgA. The quantities of PWM-stimulated IgG, IgM, or IgA secreting cells in IDDM were comparable to the controls. The IDDM patients with spontaneous immunoglobulin secreting cells had higher fasting C-peptide levels compared to the patients with immunoglobulin-producing cells within the normal range (P < 0.05). The average titre of islet cell cytoplasmic antibodies was 1:26 in (9 out of 9 were positive) patients with, compared to 1:1 in patients (4 out of 8 were positive) without spontaneous secretion (P = 0.025). These results suggest that the clinical onset of IDDM is associated with a polyclonal B lymphocyte activation and that higher levels of fasting C-peptide islet cell antibodies are associated with this immunoregulatory abnormality.

scholarly journals Reversal of infectious mononucleosis-associated suppressor T cell activity by D-mannose.

1983 ◽  
Vol 158 (4) ◽  
pp. 1048-1060 ◽  
Author(s):  
G Tosato ◽  
S E Pike ◽  
R M Blaese
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Infectious Mononucleosis ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Cell Activity ◽  
Pokeweed Mitogen ◽  
Suppressor T Cells

Epstein-Barr virus-induced infectious mononucleosis (IM) is associated with the activation of suppressor T lymphocytes that profoundly inhibit immunoglobulin (Ig) production in vitro. We have examined the nature of signals operating in the interaction between IM suppressor T cells and their targets, and explored the possibility that a lectin-like receptor molecule and its specific sugar might provide specificity to this interaction. When D-mannose or some of its derivatives, including alpha-methyl-D-mannoside, mannose-6-phosphate, and mannan, were added to suppressed cultures containing IM T lymphocytes and pokeweed mitogen (PWM)-stimulated normal mononuclear cells, a significant enhancement of Ig production was observed. These sugars had little or no effect on Ig production by the PWM-stimulated responder cells alone and thus the enhanced Ig production could be attributed to the reversal of suppression in the co-cultures by these sugars. This was further confirmed by the observation that the sugars were effective only if present during the first 24 h of culture, a time when IM suppressor T cells exert their principal effect. The effect of sugars on Ig production by suppressed cultures was similar to that achieved by decreasing by about fourfold the number of IM T cells in culture. The effect of the sugars is unlikely to represent a form of nonspecific toxicity, since inhibited cultures become responders in the presence of the sugar. Furthermore, toxicity restricted to the suppressor T cells is unlikely, since preincubation of the T cells with the sugars did not reduce their subsequent ability to suppress in secondary indicator cultures. In addition, there was no correlation between the effect of the sugars on T cell proliferation and their effect on T cell-mediated suppression. The reversal of suppression by sugars was dose dependent and demonstrated stereo-specificity in that L-mannose was without effect while D-mannose reversed suppression. These data indicate that D-mannose and some of its derivatives consistently reverse suppression of Ig production by IM T cells and strongly suggest a role for saccharides as critical components in the cellular receptors involved in certain physiologic immune cell interactions.

scholarly journals Emoxipine Modulates Concentration-Dependent Effects of Cytarabine and Cyclocytidine on Activation of Human T Cells

2021 ◽  
pp. 249-260
Author(s):  
Darya B. Nizheharodava ◽  
Eugenii I. Kvasyuk ◽  
Marina M. Zafranskaya ◽  
Aliaksei G. Sysa ◽  
Tatyna N. Zhukovets ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood ◽  
Adaptive Immune Cells ◽  
Human T Cells

Title: Emoxipine modulates concentration-dependent effects of cytarabine and cyclocytidine on activation of human T cells. Introduction: Both cytarabine and cyclocytidine are used in the treatment of acute myeloid leukemia. Well known that cytarabine and other related cytosine-based nucleoside analogues are being toxic to tumor cells by increasing levels of cellular oxidative stress as it could be abrogated by antioxidants. However, very little is known both about both the effects of combinations of antimetabolites with antioxidants on the cytotoxic innate and adaptive immune cells and whether lymphocytes toxicity affects its anticancer efficiency. Aim: To estimate effects of cytarabine and cyclocytidine with emoxipine on in vitro activated human T cells at concentrations reached during in vivo treatment with high doses, conventional doses and low doses. Materials and Methods: T cells derived from blood donors were activated in vitro in cell culture medium alone or supplemented with cytarabine 0.1-10.0 μM or cyclocytidine 0.1-10.0 μM. Cell characteristics were assessed by flow cytometry. Results: Only cytarabine 1.0-10.0 μM had both antiproliferative and proapoptotic effects. Additionally, these cytarabine concentrations increased the γIFN-producing by CD3+CD4+ T cells and did not affect the release of this cytokine by CD3+CD8+ T cells. In contrast, the lowest concentration (0.1 μM) did not have or showed minor antiproliferative or cytotoxic effects, did not alter the release of γIFN. Cyclocytidine did not affect viability of normal peripheral blood mononuclear cells but decreased the proliferative capacity of activated normal T cells in dose-dependent manner. Additionally, cyclocytidine  altered the percentage of γIFN-producing proliferative CD3+CD8+ cytotoxic T cells for any concentration tested (0.1, 1.0, 1 and 10.0 μM) meanwhile highly suppressed the number of the whole amount of CD3+CD8+ cells and did not affect the release of cytokines by CD3+CD4+ T cells. The study of the expression of the CD107a marker showed a significant stimulating effect of 10 µm of citarabine on the activation of subpopulations of T-lymphocytes (CD3+) and cytotoxic T-lymphocytes (CD3+CD8+).

scholarly journals Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of Four Plasmodium falciparum DNA Plasmids

1998 ◽  
Vol 66 (9) ◽  
pp. 4193-4202 ◽  
Author(s):  
Ruobing Wang ◽  
Denise L. Doolan ◽  
Yupin Charoenvit ◽  
Richard C. Hedstrom ◽  
Malcolm J. Gardner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
T Cell Responses ◽  
Peripheral Blood Mononuclear ◽  
Effector Cells ◽  
Cell Responses

ABSTRACT CD8+ T cells have been implicated as critical effector cells in protective immunity against malaria parasites developing within hepatocytes. A vaccine that protects against malaria by inducing CD8+ T cells will probably have to include multiple epitopes on the same protein or different proteins, because of parasite polymorphism and genetic restriction of T-cell responses. To determine if CD8+ T-cell responses against multiple P. falciparum proteins can be induced in primates by immunization with plasmid DNA, rhesus monkeys were immunized intramuscularly with a mixture of DNA plasmids encoding four P. falciparumproteins or with individual plasmids. All six monkeys immunized with PfCSP DNA, seven of nine immunized with PfSSP2 DNA, and five of six immunized with PfExp-1 or PfLSA-1 DNA had detectable antigen-specific cytotoxic T lymphocytes (CTL) after in vitro restimulation of peripheral blood mononuclear cells. CTL activity was genetically restricted and dependent on CD8+ T cells. By providing the first evidence for primates that immunization with a mixture of DNA plasmids induces CD8+ T-cell responses against all the components of the mixture, these studies provide the foundation for multigene immunization of humans.

scholarly journals The effect of serum on monocyte tissue factor generation

Blood ◽  
1984 ◽  
Vol 64 (3) ◽  
pp. 707-714 ◽  
Author(s):  
RL Edwards ◽  
D Perla
Keyword(s):  
T Cells ◽  
Tissue Factor ◽  
Mononuclear Cells ◽  
High Serum ◽  
Peripheral Blood Mononuclear ◽  
Serum Factors ◽  
Normal Peripheral Blood ◽  
Stimulatory Activity ◽  
Normal Hemostasis

Abstract Human monocytes generate the procoagulant tissue factor (MTF) following exposure to a variety of immune stimuli in vitro. The generation of MTF is modified by T cells, lymphokines, and immunoregulatory lipoproteins, and recent studies have shown that MTF can be activated in an immune- specific manner following exposure to antigen. We have examined the role of serum factors in the regulation of MTF generation. Low concentrations (less than 1%) of heat-inactivated normal human serum greatly enhanced MTF generation in cultures of normal peripheral blood mononuclear cells. The stimulatory effect was observed in cultures of both unstimulated cells and cells exposed to bacterial lipopolysaccharide. Stimulation was not observed at high serum concentrations (greater than 10%) and could not be explained by endotoxin contamination or activation of the assay system. Stimulatory activity was present in plasma and BaSO4-adsorbed plasma as well as autologous and allogeneic serum, was not abolished by removal of serum lipoproteins, and did not require the presence of T cells for its expression. Sera from 28 different normal volunteers were screened for stimulatory activity and demonstrated a wide variation in potency. These results suggest that a potent factor is present in sera that enhances the expression of MTF activity in vitro. This factor is distinct from previously described lipoprotein regulators and may play a role in the initiation of coagulation in both normal hemostasis and pathologic states.

scholarly journals The Anthrax Vaccine Adsorbed Vaccine Generates Protective Antigen (PA)-Specific CD4+ T Cells with a Phenotype Distinct from That of Naïve PA T Cells

2008 ◽  
Vol 76 (10) ◽  
pp. 4538-4545 ◽  
Author(s):  
William W. Kwok ◽  
Junbao Yang ◽  
Eddie James ◽  
John Bui ◽  
Laurie Huston ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Protective Antigen ◽  
Ex Vivo ◽  
Cytokine Profile ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear ◽  
Anthrax Vaccine ◽  
Cellular Immune

ABSTRACT Cellular immune responses against protective antigen (PA) of Bacillus anthracis in subjects that received the anthrax vaccine adsorbed (AVA) vaccine were examined. Multiple CD4+ T-cell epitopes within PA were identified by using tetramer-guided epitope mapping. PA-reactive CD4+ T cells with a CD45RA− phenotype were also detected by direct ex vivo staining of peripheral blood mononuclear cells (PBMC) with PA-specific tetramers. Surprisingly, PA-specific T cells were also detected in PBMC of nonvaccinees after a single cycle of in vitro PA stimulation. However, PA-reactive CD4+ T cells in nonvaccinees occurred at lower frequencies than those in vaccinees. The majority of PA-reactive T cells from nonvaccinees were CD45RA+ and exhibited a Th0/Th1 cytokine profile. In contrast, phenotyping and cytokine profile analyses of PA-reactive CD4+ T cells from vaccinees indicated that vaccination leads to commitment of PA-reactive T cells to a Th2 lineage, including generation of PA-specific, pre-Th2 central memory T cells. These results demonstrate that the current AVA vaccine is effective in skewing the development of PA CD4+ T cells to the Th2 lineage. The data also demonstrated the feasibility of using class II tetramers to analyze CD4+ cell responses and lineage development after vaccination.

scholarly journals Precision engineering of an anti-HLA-A2 chimeric antigen receptor in regulatory T cells for transplant immune tolerance

2021 ◽  
Author(s):  
Yannick D. Muller ◽  
Leonardo M.R. Ferreira ◽  
Emilie Ronin ◽  
Patrick Ho ◽  
Vinh Nguyen ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Chimeric Antigen Receptor ◽  
Mononuclear Cells ◽  
Antigen Receptor ◽  
Single Chain ◽  
Transplant Tolerance ◽  
Peripheral Blood Mononuclear

Infusion of regulatory T cells (Tregs) engineered with a chimeric antigen receptor (CAR) targeting donor-derived human leukocyte antigen (HLA) is a promising strategy to promote transplant tolerance. Here, we describe an anti-HLA-A2 CAR (A2-CAR) generated by grafting the complementarity-determining regions (CDRs) of a human monoclonal anti-HLA-A2 antibody into the framework regions of the Herceptin 4D5 single-chain variable fragment and fusing it with a CD28-zeta signaling domain. The CDR-grafted A2-CAR maintained the specificity of the original antibody. We then generated HLA-A2 mono-specific human CAR Tregs either by deleting the endogenous T-cell receptor (TCR) via CRISPR/Cas9 and introducing the A2-CAR using lentiviral transduction or by directly integrating the CAR construct into the TCR alpha constant locus using homology-directed repair. These A2-CAR+TCRdeficient human Tregs maintained both Treg phenotype and function in vitro. Moreover, they selectively accumulated in HLA-A2-expressing islets transplanted from either HLA-A2 transgenic mice or deceased human donors. A2-CAR+TCRdeficient Tregs did not impair the function of these HLA-A2+ islets, whereas similarly engineered A2-CAR+TCRdeficientCD4+ conventional T cells rejected the islets in less than 2 weeks. A2-CAR+TCRdeficient Tregs delayed graft-versus-host disease only in the presence of HLA-A2, expressed either by co-transferred peripheral blood mononuclear cells or by the recipient mice. Altogether, we demonstrate that genome-engineered mono-antigen-specific A2-CAR Tregs localize to HLA-A2-expressing grafts and exhibit antigen-dependent in vivo suppression, independent of TCR expression. These approaches may be applied towards developing precision Treg cell therapies for transplant tolerance.

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