Autoreactive T cells from MRL- lpr lpr mice secrete multiple lymphokines and induce the production of IgG anti-DNA antibodies

Kai Deusch, Rafael Fernandez-Botran, Manoussos Konstadoulakis, Kenneth Baur, Robert S. Schwartz, Michael P. Madaio

Research output: Contribution to journalArticle

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Abstract

The study of T cells in individuals with systemic lupus erythematosus has been limited because a specific marker for the disease has not been identified. To approach this issue, we isolated autoreactive T cell clones from lupus-prone MRL mice, a strain that develops an accelerated form of lupus. These CD4+ T cell clones grew spontaneously from unimmunized mice, and were maintained in culture by intermittent stimulation with syngeneic antigen presenting cells in the absence of exogenous antigen. One autoreactive T cell clone, termed ARTC-1, previously reported to have atypical MHC requirements for activation (both I-Ak and I-Ek were required) and to stimulate B cell proliferation and Ig production in vitro, was found to have an unrestricted pattern of lymphokine secretion. Following stimulation, it produced IL-4, IFN-γ and IL-2. ARTC-1 induced B cell proliferation both by cell contact and through secretion of soluble lymphokines. B cell proliferation by cell-cell contact was MHC restricted in a manner analogous to ARTC-1 activation by APCs; the B cell response was inhibited by both anti-I-Ak and anti-I-Ek antibodies. The ARTC-1 B cell interaction was also found to result in the production of IgG autoantibodies. These observations suggest that cells such as ARTC-1, if unregulated, could lead to B cell stimulation and autoantibody production in vivo, in the absence of exogenous stimulation. Furthermore, IFN-γ production by ARTC-1 could also result in enhanced class II expression, leading both to additional T-B cell interactions and to T cell interactions with endogenous cells capable of expressing class II antigens in other organs.

Original languageEnglish (US)
Pages (from-to)563-576
Number of pages14
JournalJournal of Autoimmunity
Volume4
Issue number4
DOIs
StatePublished - Aug 1991

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Lymphokines
Antinuclear Antibodies
B-Lymphocytes
Immunoglobulin G
T-Lymphocytes
Cell Communication
Clone Cells
Cell Proliferation
Autoantibodies
Histocompatibility Antigens Class II
Antigen-Presenting Cells
Interleukin-4
Systemic Lupus Erythematosus
Interleukin-2
Antigens
Antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Autoreactive T cells from MRL- lpr lpr mice secrete multiple lymphokines and induce the production of IgG anti-DNA antibodies. / Deusch, Kai; Fernandez-Botran, Rafael; Konstadoulakis, Manoussos; Baur, Kenneth; Schwartz, Robert S.; Madaio, Michael P.

In: Journal of Autoimmunity, Vol. 4, No. 4, 08.1991, p. 563-576.

Research output: Contribution to journalArticle

Deusch, Kai ; Fernandez-Botran, Rafael ; Konstadoulakis, Manoussos ; Baur, Kenneth ; Schwartz, Robert S. ; Madaio, Michael P. / Autoreactive T cells from MRL- lpr lpr mice secrete multiple lymphokines and induce the production of IgG anti-DNA antibodies. In: Journal of Autoimmunity. 1991 ; Vol. 4, No. 4. pp. 563-576.
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abstract = "The study of T cells in individuals with systemic lupus erythematosus has been limited because a specific marker for the disease has not been identified. To approach this issue, we isolated autoreactive T cell clones from lupus-prone MRL mice, a strain that develops an accelerated form of lupus. These CD4+ T cell clones grew spontaneously from unimmunized mice, and were maintained in culture by intermittent stimulation with syngeneic antigen presenting cells in the absence of exogenous antigen. One autoreactive T cell clone, termed ARTC-1, previously reported to have atypical MHC requirements for activation (both I-Ak and I-Ek were required) and to stimulate B cell proliferation and Ig production in vitro, was found to have an unrestricted pattern of lymphokine secretion. Following stimulation, it produced IL-4, IFN-γ and IL-2. ARTC-1 induced B cell proliferation both by cell contact and through secretion of soluble lymphokines. B cell proliferation by cell-cell contact was MHC restricted in a manner analogous to ARTC-1 activation by APCs; the B cell response was inhibited by both anti-I-Ak and anti-I-Ek antibodies. The ARTC-1 B cell interaction was also found to result in the production of IgG autoantibodies. These observations suggest that cells such as ARTC-1, if unregulated, could lead to B cell stimulation and autoantibody production in vivo, in the absence of exogenous stimulation. Furthermore, IFN-γ production by ARTC-1 could also result in enhanced class II expression, leading both to additional T-B cell interactions and to T cell interactions with endogenous cells capable of expressing class II antigens in other organs.",
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