Faculty Opinions recommendation of Targeted activation of human Vγ9Vδ2-T cells controls epstein-barr virus-induced B cell lymphoproliferative disease.

Abstract Epstein-Barr virus (EBV) is associated with several different types of aggressive non-Hodgkin lymphoma (NHL). Individuals with primary or secondary immunodeficiency are susceptible to developing B cell lymphoproliferation due to outgrowth of EBV-infected B cells that express type III latency characterized by expression of all nine latent-cycle EBV antigens. These cells would normally be susceptible to control by EBV-specific T cells, and strategies to restore EBV-specific immune responses may be effective therapeutically. EBV-associated lymphomas occurring in individuals who do not have a known immunodeficiency include NK and T malignancies with cytotoxic phenotypes, sporadic cases of B-NHL and lymphomatoid granulomatosis. These malignancies respond poorly to standard chemoradiotherapy, and immunotherapeutic or pharmacologic strategies targeting EBV are being explored.

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Analysis of the defects responsible for the impaired regulation of Epstein-Barr virus-induced B cell proliferation by rheumatoid arthritis lymphocytes. I. Diminished gamma interferon production in response to autologous stimulation.

Journal of Experimental Medicine ◽

10.1084/jem.157.1.173 ◽

1983 ◽

Vol 157 (1) ◽

pp. 173-188 ◽

Cited By ~ 101

Author(s):

F Hasler ◽

H G Bluestein ◽

N J Zvaifler ◽

L B Epstein

Keyword(s):

Cell Proliferation ◽

T Cells ◽

T Cell ◽

B Cell ◽

Epstein Barr Virus ◽

Gamma Interferon ◽

Barr Virus ◽

T Cell Regulation ◽

Epstein Barr

T cells of patients with rheumatoid arthritis (RA) do not control the rate of B lymphoblast transformation induced by Epstein-Barr virus (EBV) as efficiently as T cells from healthy individuals; thus, lymphoblast cell lines are established more readily in RA lymphocytes in vitro after EBV infection. In the present experiments, we have asked whether this T cell regulation can be reproduced by lymphocytes. We found that normal T cells, activated in allogeneic or autologous mixed leukocyte reactions (MLR), produce lymphokines that inhibit in vitro EBV-induced B cell proliferation. Allogeneic MLR supernatants inhibited EBV-induced DNA synthesis 62 +/- 4% (mean +/- SE) at 10 d post-infection, whereas autologous MLR supernatants suppressed it 50 +/- 3%. RA T cell supernatants produced in an allogeneic MLR suppressed as well as normal T cell supernatants (64 +/- 5% inhibition). In contrast, supernatants from RA autologous MLR had little inhibitory activity. EBV-induced DNA synthesis at 10 d was reduced only 8 +/- 3%, compared with the 50 +/- 3% suppressive activity of normal autologous MLR supernatants. The magnitude of the proliferative responses in the autologous MLR regenerating the lymphokines was similar in the normal and RA populations. After depletion of adherent cells from the RA auto-MLR stimulators, supernatant inhibitory activities increased to normal levels (from 11 +/- 6 [SE] to 52 +/- 6% [SE]). The inhibitory factor involved in the regulation of in vitro EBV infection is a protein with a molecular weight of approximately 50,000. Its activity is eliminated by hearing at 56 degrees C and by exposure to acid at pH 2. The inhibitory activity is blocked by mixing the MLR supernatants with a polyvalent antisera or monoclonal antibodies specific for human gamma interferon. Gamma interferon produced by activating T cells in allo- or auto-MLR can reproduce T cell-mediated regulation of EBV-induced B cell proliferation, and the failure of RA auto-MLR to generate that lymphokine parallels the defective T cell regulation of EBV-induced B cell proliferation characteristic of RA lymphoid cells.

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