In vitro IgE Synthesis Induced by Human T Cell Clones in Normal B Cells and Its Suppression by Heterogenous T Cell Populations

1987 ◽  
Vol 82 (3-4) ◽  
pp. 411-413 ◽  
Author(s):  
S. Romagnani ◽  
G.F. Del Prete ◽  
E. Maggi ◽  
M. Ricci
1988 ◽  
Vol 81 (1) ◽  
pp. 303 ◽  
Author(s):  
S. Romagnani ◽  
G.F. Del Prete ◽  
E. Maggi ◽  
P. Parronchi ◽  
A. Tiri ◽  
...  

1994 ◽  
Vol 180 (5) ◽  
pp. 1775-1784 ◽  
Author(s):  
P Life ◽  
J F Gauchat ◽  
V Schnuriger ◽  
S Estoppey ◽  
G Mazzei ◽  
...  

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.


1986 ◽  
Vol 16 (12) ◽  
pp. 1509-1514 ◽  
Author(s):  
Gianfranco Del Prete ◽  
Enrico Maggi ◽  
Donatella Macchia ◽  
Antonio Tiri ◽  
Paola Parronchi ◽  
...  

1986 ◽  
Vol 164 (3) ◽  
pp. 962-967 ◽  
Author(s):  
M F Luciani ◽  
J F Brunet ◽  
M Suzan ◽  
F Denizot ◽  
P Golstein

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.


2004 ◽  
Vol 39 (4) ◽  
pp. 525-530 ◽  
Author(s):  
Orla Duggan ◽  
Paul Hyland ◽  
Kathryn Annett ◽  
Robin Freeburn ◽  
Christopher Barnett ◽  
...  

1993 ◽  
Vol 177 (6) ◽  
pp. 1575-1585 ◽  
Author(s):  
G Aversa ◽  
J Punnonen ◽  
J E de Vries

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.


1986 ◽  
Vol 163 (3) ◽  
pp. 713-723 ◽  
Author(s):  
D Y Leung ◽  
M C Young ◽  
N Wood ◽  
R S Geha

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.


1989 ◽  
Vol 70 (6) ◽  
pp. 1513-1521 ◽  
Author(s):  
H. Bunschoten ◽  
R. J. Klapmuts ◽  
I. J. Th. M. Claassen ◽  
S. D. Reyneveld ◽  
A. D. M. E. Osterhaus ◽  
...  

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