scholarly journals T cell clones from an X-linked hyper-immunoglobulin (IgM) patient induce IgE synthesis in vitro despite expression of nonfunctional CD40 ligand.

1994 ◽  
Vol 180 (5) ◽  
pp. 1775-1784 ◽  
Author(s):  
P Life ◽  
J F Gauchat ◽  
V Schnuriger ◽  
S Estoppey ◽  
G Mazzei ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Rnase Protection Assay ◽  
Cd40 Ligand ◽  
Tnf Alpha ◽  
Rnase Protection ◽  
T Cell Clones ◽  
Cell Clones ◽  
Ige Synthesis

The induction of immunoglobulin E (IgE) switching in B cells requires at least two signals. The first is given by either of the soluble lymphokines interleukin 4 (IL-4) or IL-13, whereas the second is contact dependent. It has been widely reported that a second signal can be provided by the CD40 ligand (CD40L) expressed on the surface of T cells, mast cells, and basophils. A defect in the CD40L has been shown recently to be responsible for the lack of IgE, IgA, and IgG, characteristic of the childhood X-linked immunodeficiency, hyper IgM syndrome (HIGM1). IgE can however be detected in the serum of some HIGM1 patients. In this study, we isolated T cell clones and lines using phytohemagglutinin (PHA) and allergen, respectively, from the peripheral blood of one such patient who expressed a truncated form of CD40L, and investigated their ability to induce IgE switching in highly purified, normal tonsillar B cells in vitro. Unexpectedly, 4 of 12 PHA clones tested induced contact-dependent IgE synthesis in the presence of exogenous IL-4. These clones were also shown to strongly upregulated IL-4-induced germline epsilon RNA and formed dense aggregates with B cells. Of the four helper clones, three were CD8+, of which two were characteristic of the T helper cell 2 (Th2) subtype. Two allergen-specific HIGM1 T cell lines, both of the Th0 subtype, could also drive IgE synthesis when prestimulated using specific allergen. All clones and lines were negative for surface expression of CD40L, and the mutated form of CD40L was confirmed for a representative clone by RNase protection assay and sequencing. The IgE helper activity could not be attributed to membrane tumor necrosis factor alpha (TNF-alpha) although it was strongly expressed on activated clones, and the addition of neutralizing anti-TNF-alpha antibody did not abrogate IgE synthesis. These results therefore suggest the involvement of T cell surface molecules other than CD40L in the induction of IgE synthesis, and that these molecules may also be implicated in other aspects of T-B cell interactions.

scholarly journals The 26-kD transmembrane form of tumor necrosis factor alpha on activated CD4+ T cell clones provides a costimulatory signal for human B cell activation.

1993 ◽  
Vol 177 (6) ◽  
pp. 1575-1585 ◽  
Author(s):  
G Aversa ◽  
J Punnonen ◽  
J E de Vries
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cd4 T Cells ◽  
Plasma Membranes ◽  
Cd4 T Cell ◽  
Tnf Alpha ◽  
T Cell Clones ◽  
Cell Clones ◽  
Ige Synthesis

Interleukin 4 (IL-4) induces immunoglobulin (Ig)E and IgG4 synthesis in human B cells. In addition to IL-4, costimulatory signals provided by activated CD4+ T cells are required for productive IgG4 and IgE synthesis. Here we report that the 26-kD transmembrane form of tumor necrosis factor alpha (mTNF-alpha), which is rapidly expressed on CD4+ T cell clones after activation, contributes to the costimulatory signals resulting in IL-4-dependent Ig synthesis by B cells, including IgG4 and IgE production. mTNF-alpha expression was induced on T cell clones within 2 h after activation with concanavalin A. Peak expression was observed at 24 h, followed by a gradual decrease, but appreciable levels of mTNF-alpha were still detectable 72 h after activation. The presence of the 26-kD membrane form of TNF-alpha on activated T cell clones was confirmed by immunoprecipitation. Monoclonal antibodies (mAbs) recognizing mTNF-alpha, or the p55 TNF receptor, inhibited IgM, IgG, IgG4, and IgE synthesis induced by IL-4 and activated CD4+ T cell clones in cultures of highly purified surface IgD+ B cells. The anti-TNF-alpha mAbs also blocked Ig production in cultures in which the activated CD4+ T cell clones were replaced by their plasma membranes. Furthermore, pretreatment of the plasma membranes with anti-TNF-alpha mAbs strongly reduced their capacity to stimulate B cells to produce Ig in the presence of IL-4, indicating that the anti-TNF-alpha mAbs blocked the effects of mTNF-alpha. Anti-TNF-alpha mAbs did not affect IgM, IgG, IgG4, or IgE synthesis induced by anti-CD40 mAbs and IL-4 in the absence of CD4+ T cells, supporting the notion that the anti-TNF-alpha mAbs indeed interfered with the costimulatory, contact-mediated signal provided by T cells, or their membranes. Collectively these results indicate that mTNF-alpha, which is rapidly induced after activation of CD4+ T cells, participates in productive T-B cell interactions resulting in IL-4-induced Ig production. This is a novel property of the T cell membrane form of TNF-alpha.

539 Interleukin 4 (IL-4) is responsible for IgE synthesis induced in vitro by human T cell clones

1988 ◽  
Vol 81 (1) ◽  
pp. 303 ◽  
Author(s):  
S. Romagnani ◽  
G.F. Del Prete ◽  
E. Maggi ◽  
P. Parronchi ◽  
A. Tiri ◽  
...  
Keyword(s):  
T Cell ◽  
Interleukin 4 ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones ◽  
Ige Synthesis

scholarly journals Induction of IgE synthesis in normal human B cells. Sequential requirements for activation by an alloreactive T cell clone and IgE-potentiating factors.

1986 ◽  
Vol 163 (3) ◽  
pp. 713-723 ◽  
Author(s):  
D Y Leung ◽  
M C Young ◽  
N Wood ◽  
R S Geha
Keyword(s):  
T Cell ◽  
B Cells ◽  
Cell Clone ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
T Cell Clones ◽  
Cell Clones ◽  
T Cell Clone ◽  
Ige Synthesis ◽  
Alloreactive T Cell

Two human alloreactive T cell clones were established from a one-way mixed lymphocyte culture involving two nonatopic donors, and were assessed for their capacity to induce IgE synthesis by B cells obtained from the original stimulator. The two alloreactive T cell clones studied induced IgG but not IgE synthesis in normal B cells. However, one of the two clones, clone 2H6, induced IgE synthesis in the presence of supernatants from T cell lines derived from patients with the hyper-IgE syndrome (HIE), and enriched for T cells bearing receptors for IgE. These supernatants by themselves caused no IgE synthesis in nonatopic B cells. The potentiating factors in these supernatants were shown to bind to IgE. Time sequence experiments indicated that interaction of the B cells with the alloreactive clone 2H6 renders them responsive to the action of the IgE-potentiating factors. These results indicate that induction of IgE synthesis in normal B cells involves at least two sequential T cell derived signals. Furthermore, T cell clones are heterogenous in their capacity to provide these signals.

scholarly journals Cytolytic CD4+-T-Cell Clones Reactive to EBNA1 Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation

2003 ◽  
Vol 77 (22) ◽  
pp. 12088-12104 ◽  
Author(s):  
Sarah Nikiforow ◽  
Kim Bottomly ◽  
George Miller ◽  
Christian Münz
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Lymphoproliferative Disease ◽  
T Cell Clones ◽  
Barr Virus ◽  
Cell Clones ◽  
Epstein Barr

ABSTRACT In the absence of immune surveillance, Epstein-Barr virus (EBV)-infected B cells generate neoplasms in vivo and transformed cell lines in vitro. In an in vitro system which modeled the first steps of in vivo immune control over posttransplant lymphoproliferative disease and lymphomas, our investigators previously demonstrated that memory CD4+ T cells reactive to EBV were necessary and sufficient to prevent proliferation of B cells newly infected by EBV (S. Nikiforow et al., J. Virol. 75:3740-3752, 2001). Here, we show that three CD4+-T-cell clones reactive to the latent EBV antigen EBNA1 also prevent the proliferation of newly infected B cells from major histocompatibility complex (MHC) class II-matched donors, a crucial first step in the transformation process. EBNA1-reactive T-cell clones recognized B cells as early as 4 days after EBV infection through an HLA-DR-restricted interaction. They secreted Th1-type and Th2-type cytokines and lysed EBV-transformed established lymphoblastoid cell lines via a Fas/Fas ligand-dependent mechanism. Once specifically activated, they also caused bystander regression and bystander killing of non-MHC-matched EBV-infected B cells. Since EBNA1 is recognized by CD4+ T cells from nearly all EBV-seropositive individuals and evades detection by CD8+ T cells, EBNA1-reactive CD4+ T cells may control de novo expansion of B cells following EBV infection in vivo. Thus, EBNA1-reactive CD4+-T-cell clones may find use as adoptive immunotherapy against EBV-related lymphoproliferative disease and many other EBV-associated tumors.

scholarly journals Differential requirements of B cells from normal and allergic subjects for the induction of IgE synthesis by an alloreactive T cell clone.

1985 ◽  
Vol 162 (1) ◽  
pp. 202-214 ◽  
Author(s):  
D T Umetsu ◽  
D Y Leung ◽  
R Siraganian ◽  
H H Jabara ◽  
R S Geha
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Clone ◽  
T Cell Clones ◽  
Igg Synthesis ◽  
Cell Clones ◽  
T Cell Clone ◽  
Ige Synthesis ◽  
Alloreactive T Cell

Human T cell helper/inducer clones were used to induce IgE synthesis in B cells from both allergic and nonallergic donors. An alloreactive T cell clone, activated by recognition of specific HLA-DR antigens, stimulated peripheral blood B cells from both allergic and nonallergic donors to synthesize IgE antibody. B cells of allergic donors differed from those of nonallergic donors in their requirements for induction of IgE synthesis. Induction of IgE synthesis in B cells from nonallergic individuals occurred only under conditions of cognate interaction, in which the B cells expressed the alloantigen recognized by the T cells. In contrast, IgE synthesis in B cells from allergic donors occurred under conditions of cognate interaction with T cells as well as bystander conditions where the B cells did not express the alloantigen recognized by the T cell clones and where the T cell clones were stimulated by third-party monocytes bearing the relevant alloantigens. Furthermore, bystander stimulation of IgE synthesis in allergic donors occurred in the presence of tetanus toxoid (TT) antigen-specific T cell clones activated by the appropriate TT-pulsed monocytes. In contrast to the differing requirements of B cells from normal vs. allergic subjects for the induction of IgE synthesis, these B cells did not differ in their requirements for the induction of IgG synthesis. IgG synthesis was induced in all B cells under conditions of cognate interaction with the T cells as well as under conditions of bystander stimulation. These results suggest that cognate T-B cell interactions may be important in the development of IgE immune responses in the normal host.

Human T cell clones can inducein vitro IgE synthesis in normal B cells regardless of alloantigen recognition or specificity for peculiar antigens

1986 ◽  
Vol 16 (12) ◽  
pp. 1509-1514 ◽  
Author(s):  
Gianfranco Del Prete ◽  
Enrico Maggi ◽  
Donatella Macchia ◽  
Antonio Tiri ◽  
Paola Parronchi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones ◽  
Ige Synthesis

scholarly journals Self-sparing of long-term in vitro-cloned or uncloned cytotoxic T lymphocytes.

1986 ◽  
Vol 164 (3) ◽  
pp. 962-967 ◽  
Author(s):  
M F Luciani ◽  
J F Brunet ◽  
M Suzan ◽  
F Denizot ◽  
P Golstein
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cytotoxic T Cell ◽  
Cell Populations ◽  
Con A ◽  
T Cell Clones ◽  
Cell Clones

At least some long-term in vitro-cultured cytotoxic T cell clones and uncloned cell populations are able, in the presence of Con A, to lyse other cells, to be lysed by other cells, but not to lyse themselves. This as-yet-unexplained result may have implications as to the mechanism of T cell-mediated cytotoxicity.

scholarly journals Generation of Cytomegalovirus-Specific Human T-Lymphocyte Clones by Using Autologous B-Lymphoblastoid Cells with Stable Expression of pp65 or IE1 Proteins: a Tool To Study the Fine Specificity of the Antiviral Response

2000 ◽  
Vol 74 (9) ◽  
pp. 3948-3952 ◽  
Author(s):  
Christelle Retière ◽  
Virginie Prod'homme ◽  
Berthe-Marie Imbert-Marcille ◽  
Marc Bonneville ◽  
Henri Vié ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Receptor ◽  
Relevant Information ◽  
In Vitro Models ◽  
T Cell Clones ◽  
Fine Specificity ◽  
Early Protein ◽  
Cell Clones ◽  
Human T Lymphocyte

ABSTRACT Cytotoxic T lymphocytes (CTLs) play a central role in the control of persistent human cytomegalovirus (HCMV) infection in healthy virus carriers. Previous analyses of the specificity of HCMV-reactive CD8+ CTLs drawn from in vitro models in which antigen-presenting cells were autologous fibroblasts infected with laboratory HCMV strains have shown focusing of CTL responses against the major tegument protein, pp65. By contrast, the 72-kDa major immediate-early protein (IE1) was identified as a minor target for this response. Here we have studied the fine specificity and T-cell-receptor features of T-cell clones generated against autologous B lymphoblastoid cell lines stably transfected with HCMV cDNA coding for either pp65 or a natural variant of IE1. This strategy allowed efficient generation of T-cell clones against IE1 and pp65 and led to the identification of several new IE1 and pp65 epitopes, including some located in polymorphic regions of IE1. Such an approach may provide relevant information about the characteristics of the CTL response to IE1 and the effect of viral polymorphism on the immune response against HCMV.

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