scholarly journals Distinct cell surface ligands mediate T lymphocyte attachment and rolling on P and E selectin under physiological flow.

1994 ◽  
Vol 127 (5) ◽  
pp. 1485-1495 ◽  
Author(s):  
R Alon ◽  
H Rossiter ◽  
X Wang ◽  
T A Springer ◽  
T S Kupper
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Antigen Expression ◽  
Lymphocyte Antigen ◽  
Selectin Ligands ◽  
Distinct Cell ◽  
Cutaneous Lymphocyte Antigen

Memory T lymphocytes extravasate at sites of inflammation, but the mechanisms employed by these cells to initiate contact and tethering with endothelium are incompletely understood. An important part of leukocyte extravasation is the initiation of rolling adhesions on endothelial selectins; such events have been studied in monocytes and neutrophils but not lymphocytes. In this study, the potential of T lymphocytes to adhere and roll on endothelial selectins in vitro was investigated. We demonstrate that T cells can form tethers and rolling adhesions on P selectin and E selectin under physiologic flow conditions. Tethering and rolling on P selectin was independent of cell-surface cutaneous lymphocyte antigen (CLA) expression, which correlated strictly with the capacity of T cells to form rolling adhesions under flow on E selectin. T cell tethering to P selectin was abolished by selective removal of cell surface sialomucins by a P. haemolytica O-glycoprotease, while cutaneous lymphocyte antigen expression was unaffected. A sialomucin molecule identical or closely related to P selectin glycoprotein ligand-1 (PSGL-1), the major P selectin ligand on neutrophils and HL-60 cells, appears to be a major T cell ligand for P selectin. P selectin glycoprotein ligand-1 does not appear to support T cell rolling on E selectin. In turn, E selectin ligands do not appear to be associated with sialomucins. These data demonstrate the presence of structurally distinct ligands for P or E selectins on T cells, provide evidence that both ligands can be coexpressed on a single T cell, and mediate tethering and rolling on the respective selectins in a mutually exclusive fashion.

scholarly journals Quantitative assessment of the pool size and subset distribution of cytolytic T lymphocytes within human resting or alloactivated peripheral blood T cell populations.

1983 ◽  
Vol 158 (2) ◽  
pp. 571-585 ◽  
Author(s):  
A Moretta ◽  
G Pantaleo ◽  
L Moretta ◽  
M C Mingari ◽  
J C Cerottini
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Great Majority ◽  
T Cell Subsets ◽  
Cytolytic T Lymphocytes ◽  
Subset Distribution

In order to directly assess the distribution of cytolytic T lymphocytes (CTL) and their precursors (CTL-P) in the two major subsets of human T cells, we have used limiting dilution microculture systems to determine their frequencies. The two subsets were defined according to their reactivity (or lack thereof) with B9.4 monoclonal antibody (the specificity of which is similar, if not identical, to that of Leu 2b monoclonal antibody). Both B9+ and B9- cells obtained by sorting peripheral blood resting T cells using the fluorescence-activated cell sorter (FACS) were assayed for total CTL-P frequencies in a microculture system that allows clonal growth of every T cell. As assessed by a lectin-dependent assay, approximately 30% of peripheral blood T cells were CTP-P. In the B9+ subset (which represents 20-30% of all T cells), the CTL-P frequency was close to 100%, whereas the B9- subset had a 25-fold lower CTL-P frequency. It is thus evident that 90% and 10% of the total CTL-P in peripheral blood are confined to the B9+ or B9- T cell subsets, respectively. Analysis of the subset distribution of CTL-P directed against a given set of alloantigens confirmed these findings. CTL-P frequencies were also determined in B9+ and B9- subsets derived from T cells that had been activated in allogenic mixed leucocyte cultures (MLC). Approximately 10% of MLC T cells were CTL-P. This frequency was increased 3.5-fold in the B9+ subset, whereas the B9- subset contained only a small, although detectable number of CTL-P. Moreover, the great majority of the (operationally defined) CTL-P in MLC T cell population were found to be directed against the stimulating alloantigens, thus indicating a dramatic increase in specific CTL-P frequencies following in vitro stimulation in bulk cultures.

scholarly journals Immune function of the blood-brain barrier: incomplete presentation of protein (auto-)antigens by rat brain microvascular endothelium in vitro.

1990 ◽  
Vol 110 (5) ◽  
pp. 1757-1766 ◽  
Author(s):  
W Risau ◽  
B Engelhardt ◽  
H Wekerle
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Rat Brain ◽  
Blood Brain Barrier ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ifn Gamma

The endothelial blood-brain barrier (BBB) has a critical role in controlling lymphocyte traffic into the central nervous system (CNS), both in physiological immunosurveillance, and in its pathological aberrations. The intercellular signals that possibly could induce lymphocytes to cross the BBB include immunogenic presentation of protein (auto-)antigens by BBB endothelia to circulating T lymphocytes. This concept has raised much, though controversial, attention. We approached this problem by analyzing in vitro immunospecific interactions between clonal rat T lymphocyte lines with syngeneic, stringently purified endothelial monolayer cultures from adult brain micro-vessels. The rat brain endothelia (RBE) were established from rat brain capillaries using double collagenase digestion, density gradient fractionation and selective cytolysis of contaminating pericytes by anti-Thy 1.1 antibodies and complement. Incubation with interferon-gamma in most of the brain-derived endothelial cells induced Ia-antigens in the cytoplasm and on the cell surface in some of the cells. Before the treatment, the cells were completely Ia-negative. Pericytes were unresponsive to IFN-gamma treatment. When confronted with syngeneic T cell lines specific for protein (auto-)antigens (e.g., ovalbumin and myelin basic protein, MBP), RBE were completely unable to induce antigen-specific proliferation of syngeneic T lymphocytes irrespective of pretreatment with IFN-gamma and of cell density. RBE were inert towards the T cells, and did not suppress T cell activation induced by other "professional" antigen presenting cells (APC) such as thymus-derived dendritic cells or macrophages. IFN-gamma-treated RBE were, however, susceptible to immunospecific T cell killing. They were lysed by MBP-specific T cells in the presence of the specific antigen or Con A. Antigen dependent lysis was restricted by the appropriate (MHC) class II product. We conclude that the interaction of brain endothelial cells with encephalitogenic T lymphocytes may involve recognition of antigen in the molecular context of relevant MHC products, but that this interaction per se is insufficient to initiate the full T cell activation program.

Insights into the ontogeny and activation of T cells

1994 ◽  
Vol 40 (11) ◽  
pp. 2128-2131 ◽  
Author(s):  
T W Mak
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Immune Responses ◽  
Tyrosine Phosphatase ◽  
T Cell Development ◽  
Cell Development ◽  
Mutant Mice ◽  
Target Cells

Abstract T lymphocytes recognize antigen peptides and major histocompatibility complex products through their T-cell antigen receptors (TcR), consisting of alpha and beta chains. The interaction between T cells and their target cells or antigen-presenting cells is also assisted by a series of other cell-surface polypeptides, most notably CD4 and CD8, which are selectively expressed on mature helper/inducer and killer/suppressor T cells, respectively. Upon engagement of their ligands, a series of signals is transduced intracytoplasmically via some of these molecules and their associated proteins. Perhaps the most important enzyme in this signal transduction process is the lymphocyte-specific tyrosine kinase lck. Another important component is the cell-surface tyrosine phosphatase CD45. This molecule is alternatively spliced and the different isoforms are expressed on the various hematopoietic and lymphopoietic cells. Signaling through the TcR-CD4 D8-lck-CD45 complex is thought to be insufficient to activate T lymphocytes. A costimulatory signal is believed to be essential, and many investigators have suggested that CD28, a ligand for B7/BB1, is such a signal. Immune responses are also controlled by a number of cytokines and soluble factors. Signaling through the tumor necrosis factor receptor p55 is required for clearance of intracellular pathogens. Transcriptional factors involved in controlling interferon production are also important in T-cell development and immune responses. In an attempt to gain a better understanding of the roles of these molecules in T-lymphocyte functions and ontogeny, we generated a series of mutant mice with disruptions in the genes coding for these molecules. We are analyzing the mutant mice to evaluate the importance of these genes in T-cell development.

Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression

Blood ◽  
2002 ◽  
Vol 99 (6) ◽  
pp. 2084-2093 ◽  
Author(s):  
Alexander D. McLellan ◽  
Michaela Kapp ◽  
Andreas Eggert ◽  
Christian Linden ◽  
Ursula Bommhardt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Antigen Expression ◽  
Cell Receptor ◽  
In Vitro Assays ◽  
Peptide Complexes ◽  
Marginal Zones

Abstract Mouse spleen contains CD4+, CD8α+, and CD4−/CD8α− dendritic cells (DCs) in a 2:1:1 ratio. An analysis of 70 surface and cytoplasmic antigens revealed several differences in antigen expression between the 3 subsets. Notably, the Birbeck granule–associated Langerin antigen, as well as CD103 (the mouse homologue of the rat DC marker OX62), were specifically expressed by the CD8α+ DC subset. All DC types were apparent in the T-cell areas as well as in the splenic marginal zones and showed similar migratory capacity in collagen lattices. The 3 DC subtypes stimulated allogeneic CD4+ T cells comparably. However, CD8α+ DCs were very weak stimulators of resting or activated allogeneic CD8+ T cells, even at high stimulator-to-responder ratios, although this defect could be overcome under optimal DC/T cell ratios and peptide concentrations using CD8+ F5 T-cell receptor (TCR)–transgenic T cells. CD8α− or CD8α+DCs presented alloantigens with the same efficiency for lysis by cytotoxic T lymphocytes (CTLs), and their turnover rate of class I–peptide complexes was similar, thus neither an inability to present, nor rapid loss of antigenic complexes from CD8α DCs was responsible for the low allostimulatory capacity of CD8α+ DCs in vitro. Surprisingly, both CD8α+ DCs and CD4−/CD8− DCs efficiently primed minor histocompatibility (H-Y male antigen) cytotoxicity following intravenous injection, whereas CD4+ DCs were weak inducers of CTLs. Thus, the inability of CD8α+ DCs to stimulate CD8+ T cells is limited to certain in vitro assays that must lack certain enhancing signals present during in vivo interaction between CD8α+ DCs and CD8+ T cells.

scholarly journals Partial immunologic reconstitution of a patient with acquired agammaglobulinemia: a transient phenomenon accompanying therapeutic plasmapheresis

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 233-235 ◽  
Author(s):  
B Wenz ◽  
A Rubinstein
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Clinical Remission ◽  
Helper T Cells ◽  
Transient Phenomenon ◽  
Helper Activity ◽  
Immunologic Reconstitution ◽  
Cell Defect

Abstract A patient with acquired agammaglobulinemia was treated with plasmapheresis. The rationale for this procedure was based on the presence of a cytotoxic autoantibody with specificity for helper (TH2-) T lymphocytes. Plasmapheresis reduced the autoantibody concentration to undetectable levels, which resulted in an increase number of helper T cells. These T cells provided normal in vitro helper activity. Plasmapheresis did not correct a concomitant suppressor T-cell defect, and the clinical remission ended during the fifth month of exchange therapy.

scholarly journals SBF-1 inhibits contact hypersensitivity in mice through down-regulation of T-cell-mediated responses

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Wei Chen ◽  
Xianying Fang ◽  
Yuan Gao ◽  
Ke Shi ◽  
Lijun Sun ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Contact Hypersensitivity ◽  
Immunosuppressive Activity ◽  
Con A ◽  
Activated T Cells ◽  
Picryl Chloride

Abstract Background T lymphocytes play an important role in contact hypersensitivity. This study aims to explore the immunosuppressive activity of SBF-1, an analog of saponin OSW-1, against T lymphocytes in vitro and in vivo. Methods Proliferation of T lymphocytes from lymph nodes of mice was determined by MTT assay. Flow cytometry analysis was performed to assess T cell activation and apoptosis. Levels of cytokines were determined by PCR and ELISA. BALB/c mice were sensitized and challenged with picryl chloride and thickness of left and right ears were measured. Results SBF-1 effectively inhibited T lymphocytes proliferation induced by concanavalin A (Con A) or anti-CD3 plus anti-CD28 at a very low dose (10 nM) but exhibited little toxicity in non-activated T lymphocytes at concentrations up to 10 μM. In addition, SBF-1 inhibited the expression of CD25 and CD69, as well as he phosphorylation of AKT in Con A-activated T cells. SBF-1 also induced apoptosis of activated T cells. In addition, SBF-1 also downregulated the induction of the T cell cytokines, IL-2 and IFN-γ in a dose-dependent manner. Furthermore, SBF-1 significantly suppressed ear swelling and inflammation in a mouse model of picryl chloride-induced contact hypersensitivity. Conclusions Our findings suggest that SBF-1 has an unique immunosuppressive activity both in vitro and in vivo mainly through inhibiting T cell proliferation and activation. Its mechanism appears to be related to the blockage of AKT signaling pathway.

Analysis of Memory T Lymphocytes Activity Following Stimulation with HLA-A24, A1 and Cw4 Restricted 9- and 10-mer Cytomegalovirus pp65 Overlapping Peptides.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2876-2876
Author(s):  
Monica Ghei ◽  
David F. Stroncek ◽  
Maurizio Provenzano
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Immune Therapy ◽  
Hla Class I ◽  
Class I ◽  
Specific Ctls ◽  
Over Time

Abstract In healthy subjects, primary infection with Cytomegalovirus (CMV) is usually mild or asymptomatic and is effectively controlled by the cell-mediated immune response. However, in immune compromised individuals, such as those with AIDS or after bone marrow transplantation, CMV reactivation is associated with significant morbidity until the individual’s immune system is completely reconstituted. One means of preventing post-transplant CMV infection is adoptive immunotherapy using CMV-specific cytotoxic T cells (CTLs) from the transplant donor. Several 9- and 10-mer HLA class I restricted peptides derived from the immune dominant CMV 65 kd matrix phosphoprotein (pp65) have been shown to produce CMV-specific CTLs. Two overlapping HLA-A24 restricted peptides have been specifically described: pp65 341–349 and pp65 341–350. These are 9- and 10-mer peptides that overlap except for the last amino acid phenylalanine (F) at the C-terminus [QYDPVAALF(F)]. Despite their similarity, the ability of these peptides to induce a T cell response has been reported to differ. Although it has been generally accepted that a unique CMV peptide is bound and presented by each separate HLA class I molecule, recent studies suggest that certain peptides are more promiscuous and may be presented by more than one HLA Class I antigen. For example, the 9-mer pp65 341–349 has been shown to stimulate CTLs from both HLA-A24 and Cw4 donors, while the 10-mer pp65 341–350 has been shown to be reactive with both HLA-A24 and A1 donors. The current investigation sought to compare the potency of these two peptides and determine the optimum peptide size for effective CMV adoptive immune therapy. Both peptides were tested for their ability to stimulate CMV-specific CTLs in HLA-A24, HLA-A1, and HLA-Cw4 restriction. In addition, a pp65 16-mer that included the 9- and 10-mers was tested for its ability to reactivate either CD8+ or CD4+ memory T cells. IFN-γ mRNA transcript as well as protein production were measured by in vitro cell culture assays. Peptide stimulations were performed on isolated CD8 and CD4 T lymphocytes by inducing the cells for 3 hours after a 2-week in vitro sensitization. The goal of the investigation was to determine whether both the 9- and the 10-mer peptides maintained high levels of CTL stimulation over time for all HLA restrictions studied. Moreover, it was important to investigate whether stimulation with the 16-mer, followed by restimulation by the two smaller peptides embedded within the larger sequence, led to effective T cell memory immune response. The 9- and 10-mer peptides effectively stimulated CTLs from HLA-A24, HLA-A1, and HLA-Cw4 CMV seropositive donors. Although both 9- and 10-mer were able to maintain high levels of stimulation over time for all restrictions, the 9-mer induced highest responses in cells expressing HLA-A24 (S.I. 4.07–528) or HLA-Cw4 (S.I. 4.15–483) while the 10-mer induced highest responses in cells expressing HLA-A24 (S.I. 3.5–528) or HLA-A1 (S.I. 8.25–615). The 16-mer peptide was also able to stimulate T cells from all HLA-A24, A1 and Cw4 donors (S.I. 6.95, 4.96, 5.02) at levels that are well maintained over time. This data confirmed that both the 9- and the 10-mer peptides are promiscuous and not restricted to a single HLA antigen. These peptides that have the ability to produce CMV-specific CTLs in patients with several different HLA types present a practical advantage over peptides that are restricted only to a single HLA type, and thus are optimal for CMV adoptive immune therapy.

scholarly journals Elimination of syngeneic sarcomas in rats by a subset of T lymphocytes.

1980 ◽  
Vol 152 (4) ◽  
pp. 823-841 ◽  
Author(s):  
E Fernandez-Cruz ◽  
B A Woda ◽  
J D Feldman
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Subset ◽  
Suppressor Cells ◽  
Effector Cells ◽  
Long Duration ◽  
Ia Antigens

Established subcutaneous Moloney sarcomas (MST-1) of large size and long duration were eliminated from syngeneic rats by intravenous infusion of varying numbers of specific syngeneic effector T lymphocytes. Spleen cells from BN rats in which tumor had regressed were cultured in an in vitro mixed lymphocyte tumor cell culture (MLTC) to augment cytotoxicity of effector cells. In the MLTC a T cell subset was expanded in response to MST-1 antigens and transformed into blast elements. With these changes, there was an increase in the W3/25 antigen on the T cell surface, a decrease of W3/13 antigen, and an increase in the number of T cells with Ia antigens. The subset associated with elimination of established tumors was a blast T cell W3/25+, W3/13+, as detected by monoclonal antibodies to rat T antigens. The W3/25+ subset was poorly cytotoxic in vitro for MST-1 and apparently functioned in vivo as an amplifier or helper cell in the tumor-bearing host. The W3/25- population was a melange of cells that included (W3/13+, W3/25-) T cells, null cells, Ig+ cells, and macrophages, and was associated with enhancement of tumor in vivo, suggesting the presence of suppressor cells.

scholarly journals New differentiation pathway for double-negative regulatory T cells that regulates the magnitude of immune responses

Blood ◽  
2006 ◽  
Vol 109 (9) ◽  
pp. 4071-4079 ◽  
Author(s):  
Dong Zhang ◽  
Wei Yang ◽  
Nicolas Degauque ◽  
Yan Tian ◽  
Allison Mikita ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Surface ◽  
Immune Responses ◽  
Lymphoid Tissues ◽  
Double Negative ◽  
Healthy Humans

Abstract Recent studies have demonstrated that in peripheral lymphoid tissues of normal mice and healthy humans, 1% to 5% of αβ T-cell receptor–positive (TCR+) T cells are CD4−CD8− (double-negative [DN]) T cells, capable of down-regulating immune responses. However, the origin and developmental pathway of DN T cells is still not clear. In this study, by monitoring CD4 expression during T-cell proliferation and differentiation, we identified a new differentiation pathway for the conversion of CD4+ T cells to DN regulatory T cells. We showed that the converted DN T cells retained a stable phenotype after restimulation and that furthermore, the disappearance of cell-surface CD4 molecules on converted DN T cells was a result of CD4 gene silencing. The converted DN T cells were resistant to activation-induced cell death (AICD) and expressed a unique set of cell-surface markers and gene profiles. These cells were highly potent in suppressing alloimmune responses both in vitro and in vivo in an antigen-specific manner. Perforin was highly expressed by the converted DN regulatory T cells and played a role in DN T-cell–mediated suppression. Our findings thus identify a new differentiation pathway for DN regulatory T cells and uncover a new intrinsic homeostatic mechanism that regulates the magnitude of immune responses. This pathway provides a novel, cell-based, therapeutic approach for preventing allograft rejection.

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