Autoreactive T cells from MRL-lpr/lpr mice secrete multiple lymphokines and induce the production of IgG anti-DNA antibodies.
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-gamma 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-gamma 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.
Deusch
K
K
Department of Medicine New England Medical Center, Boston, MA.
Fernandez-Botran
R
R
Konstadoulakis
M
M
Baur
K
K
Schwartz
R S
RS
Madaio
M P
MP
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D006649:Histocompatibility Antigens / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000974:Antibodies, Antinuclear; D006649:Histocompatibility Antigens; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D007376:Interleukin-2; D008222:Lymphokines; D015847:Interleukin-4; D007371:Interferon-gamma