Generation of human T-cell hybrids with the characteristics of human peripheral blood T-lymphocytes

1983 ◽  
Vol 6 (4) ◽  
pp. 203-207 ◽  
Author(s):  
G. Gallagher ◽  
W.H. Stimson
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Cell Hybrids ◽  
Human T Cell

Differential chemokine expression profiles in human peripheral blood T lymphocytes: dependence on T-cell coreceptor and calcineurin signaling

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 216-225 ◽  
Author(s):  
Anthony D. Cristillo ◽  
Mirtha J. Macri ◽  
Barbara E. Bierer
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Signaling Pathways ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Expression Profiles ◽  
Lymphoid Tissues ◽  
Rnase Protection ◽  
Chemokine Expression ◽  
Calcineurin Activity

Abstract The chemokine superfamily consists of small (8-10 kDa) molecules that function to attract, selectively, different subsets of leukocytes. Binding of chemokines to their appropriate G-protein–coupled receptors is necessary for primary immune responses and for homing of leukocytes to lymphoid tissues. Here, we have characterized the signaling pathways in primary T lymphocytes that regulate chemokine gene induction using an RNase protection assay. Dependence on stimulation through the coreceptor CD28 and sensitivity to the calcineurin inhibitors cyclosporine and tacrolimus were studied using purified human peripheral blood lymphocytes. Lymphotactin (Ltn), macrophage inflammatory protein (MIP)–1α, and MIP-1β were all rapidly induced and sensitive to cyclosporine treatment. At later time points, the expression of MIP-1α and MIP-1β, but not of Ltn, was restored despite the inhibition of calcineurin activity. By contrast, the induction of interleukin-8 was delayed and was found to be cyclosporine insensitive. Calcineurin activity of IP-10 mRNA induction was contingent on the specific T-cell stimulation conditions, suggesting that IP-10 expression is modulated by calcineurin-dependent and -independent signaling pathways. Differential chemokine expression profiles result from the engagement of T-cell coreceptors and the requirement for, and the dependence on, calcineurin phosphatase activity.

scholarly journals Distinct molecular forms of human T cell receptor gamma/delta detected on viable T cells by a monoclonal antibody.

1988 ◽  
Vol 167 (5) ◽  
pp. 1625-1644 ◽  
Author(s):  
J Borst ◽  
J J van Dongen ◽  
R L Bolhuis ◽  
P J Peters ◽  
D A Hafler ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Cell Lineage ◽  
Cell Receptor ◽  
Cytolytic Activity ◽  
Molecular Forms ◽  
Gamma Delta ◽  
Gamma Chain ◽  
Human T Cell

A second type of TCR molecule has been identified on human and murine T lymphocytes, which involves the protein products of the gamma and delta genes. T lymphocytes bearing this receptor may constitute a separate cell lineage with a distinct immune function. We have produced an mAb, which specifically detects human TCR-gamma/delta in native as well as denatured states, this in contrast to previously used anti-gamma chain peptide sera, which only reacted with denatured protein. The receptor occurs in different molecular forms, with or without interchain disulphide bonds, in which a delta chain may or may not be detected by cell surface iodination. The mAb is reactive with all these receptor forms. Therefore, this antibody could be used to determine the expression of TCR-gamma/delta on viable human T lymphocytes. In normal individuals, TCR-gamma/delta was found on a subset composing 2-7% of CD3+ lymphocytes in peripheral blood and 0.1-1.0% in thymus. The majority of these cells do not express the CD4 or CD8 antigens, although a significant percentage of CD8+ cells was found. TCR-gamma/delta+ cells in peripheral blood are resting lymphocytes, as judged by ultrastructural analysis. T cell clones with different receptor types can display MHC-nonrestricted cytolytic activity, which is shown to be induced by the culture conditions, most likely by growth factors such as IL-2. This strongly suggests that TCR-gamma/delta does not play a role in target cell recognition in MHC-nonrestricted cytotoxicity. The anti-TCR-gamma/delta antibody can specifically induce cytotoxic activity in clones expressing the receptor, but in addition inhibit growth factor induced cytotoxicity, which indicates a regulatory role of the TCR-gamma/delta/CD3 complex in MHC-nonrestricted cytotoxicity.

scholarly journals Human natural killer cells isolated from peripheral blood do not rearrange T cell antigen receptor beta chain genes.

1986 ◽  
Vol 163 (1) ◽  
pp. 209-214 ◽  
Author(s):  
L L Lanier ◽  
S Cwirla ◽  
N Federspiel ◽  
J H Phillips
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Antigen Receptor ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Beta Chain Genes

The lineage of NK cells and their relationship to T lymphocytes have been controversial issues. Since rearrangement of the T cell antigen receptor beta chain genes occurs early in the ontogeny and differentiation of all T cells, this can be used as an unequivocal marker to discriminate T from non-T lymphocytes. Recent studies (16-18) examining T cell antigen receptor gene rearrangement and expression in certain IL-2-dependent NK cell lines and leukemias have revealed that some lines rearrange C beta genes, whereas others do not. However, it is important to establish whether these cell lines are representative of the major population of NK cells freshly derived from the host. Herein, we have purified granulocytes, CD16+ NK cells and T lymphocytes from human peripheral blood, prepared genomic DNA from each cell type, and then examined the organization of their T cell antigen receptor genes by restriction enzyme analysis using a C beta cDNA as probe. The C beta genes were in germline configuration in NK cells and granulocytes. In contrast, peripheral blood T lymphocytes showed rearrangement of the C beta gene. These data support the hypothesis that the majority of human peripheral blood NK cells are fundamentally distinct from T lymphocytes in lineage and nonself recognition.

scholarly journals Establishing Phenotypic Features Associated with Morbidity in Human T-Cell Lymphotropic Virus Type 1 Infection

2004 ◽  
Vol 11 (6) ◽  
pp. 1105-1110 ◽  
Author(s):  
G. E. A. Brito-Melo ◽  
J. G. Souza ◽  
E. F. Barbosa-Stancioli ◽  
A. B. F. Carneiro-Proietti ◽  
B. Catalan-Soares ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
T Lymphocytes ◽  
B Cell ◽  
Virus Type ◽  
Peripheral Blood ◽  
Cell Ratio ◽  
Human T Cell ◽  
Hla Dr

ABSTRACT The human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HT). Although it is widely believed that virus infection and host immune response are involved in the pathogenic mechanisms, the role of the immune system in the development and/or maintenance of HT remains unknown. We performed an analysis of the peripheral blood leukocyte phenotype for two different subcohorts of HTLV-1-infected individuals to verify the existence of similar immunological alterations, possible laboratory markers for HT. The leukocyte population balance, the activation status of the T lymphocytes, and the cellular migratory potential of T lymphocytes, monocytes, and neutrophils were evaluated in the peripheral blood of HTLV-1-infected individuals classified as asymptomatic individuals, oligosymptomatic individuals, and individuals with HT. Data analysis demonstrated that a decreased percentage of B cells, resulting in an increased T cell/B cell ratio and an increase in the CD8+ HLA-DR+ T lymphocytes, exclusively in the HT group could be identified in both subcohorts, suggesting its possible use as a potential immunological marker for HT for use in the laboratory. Moreover, analysis of likelihood ratios showed that if an HTLV-1-infected individual demonstrated B-cell percentages lower than 7.0%, a T cell/B cell ratio higher than 11, or a percentage of CD8+ HLA-DR+ T lymphocytes higher than 70.0%, this individual would have, respectively, a 12-, 13-, or 22-times-greater chance of belonging to the HT group. Based on these data, we propose that the T cell/B cell ratios and percentages of circulating B cells and activated CD8+ T lymphocytes in HTLV-1-infected patients are important immunological indicators which could help clinicians monitor HTLV-1 infection and differentiate the HT group from the asymptomatic and oligosymptomatic groups.

scholarly journals Characterization of a novel HTLV-infected cell line

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 482-490 ◽  
Author(s):  
HP Koeffler ◽  
IS Chen ◽  
DW Golde
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Line ◽  
B Lymphocytes ◽  
Peripheral Blood ◽  
Infected Cell Line ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell

A man from Chile developed an aggressive mature T cell leukemia associated with marked eosinophilia. The neoplastic lymphocytes were of T helper surface phenotype, and they expressed the p24 and p19 antigens of human T cell leukemia virus (HTLV). A cell line (ME) was established from the patient's peripheral blood cells that was initially composed of eosinophils and T and B lymphocytes. The B lymphocytes of the cell line are polyclonal and contain Epstein-Barr virus (EBV) DNA. Many of the T lymphocytes, a few of the B lymphocytes, and none of the eosinophils express HTLV p19 and p24 antigens. By 6 months of culture, the ME line no longer contained eosinophils. A variant line of ME was established; this variant (ME-2) is notable because the cells (greater than 80%) adhere tightly to the bottom of the culture flask; they do not express T lymphocyte markers, but 30% of the cells contain cytoplasmic mu heavy immunoglobulin chains. These pre-B and null lymphocytes contain p19 and p24 antigens (80% of cells), have the HTLV- I genome, and are able to transform normal T lymphocytes in vitro. We isolated a B lymphocyte clone (11A) from ME that expresses cytoplasmic immunoglobulin (70% of cells) and p19 and p24 antigens (75% of cells), contains the EBV and HTLV genomes, and can transform T lymphocytes from normal volunteers. These data show that B lymphocytes can be infected with HTLV, although no disease of HTLV-infected B lymphocytes has been reported. The T lymphocytes from normal adult peripheral blood were easily immortalized (about 70% efficiency) by cocultivation with lethally irradiated ME cells. Twenty-five of 27 of the transformant lines were composed of T lymphocytes with helper antigens, and two of the lines were of T suppressor antigen phenotype. All the cell lines that were tested constitutively produce lymphokines, including colony- stimulating factor (CSF), erythroid-potentiating activity (EPA), macrophage migration-inhibitory factory (MIF), neutrophil-inhibitory factor (NIF), and differentiation-inducing factor (DIF).

scholarly journals Human mature T cells that are anergic in vivo prevail in SCID mice reconstituted with human peripheral blood.

1992 ◽  
Vol 175 (2) ◽  
pp. 503-516 ◽  
Author(s):  
M Tary-Lehmann ◽  
A Saxon
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Critical Role ◽  
Scid Mice ◽  
Human T Cell ◽  
Human T Cells ◽  
T Cell Lines

In these studies we have characterized the human cells that repopulate severe combined immunodeficient (SCID) mice after injection of adult peripheral blood or cord blood (hu-PBL-SCID mice). In all organs of the chimeras, and at any time point tested, single-positive (CD4+ or CD8+) T cells that expressed the alpha/beta T cell receptor (TCR) prevailed. All T cells were CD45RO+ and the majority were also HLA-DR+. Thus, the human T cells in the chimeras exhibited the phenotype of mature, memory cells that showed signs of recent activation. Cell cycle studies revealed a mitotically active human T cell population in the murine host. However, when freshly isolated from the chimeras, the human T cells were refractory to stimulation by anti-CD3 antibody but proliferated in response to exogenous interleukin 2. Chimera-derived human T cell lines retained this state of unresponsiveness to TCR-triggered proliferation for 4-6 wk in vitro. Subsequently, the T cell lines developed responses to anti-CD3 stimulation and 9 of 11 of the lines also proliferated in response to splenic stimulator cells of SCID mice. These data demonstrate that the human T cells are in a state of reversible anergy in the murine host and that xenoreactivity might play a critical role in hu-PBL-SCID mice. Mechanisms that may determine repopulation of SCID mice with human peripheral blood mononuclear cells are discussed.

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