The role of the interleukin-2 (IL-2)/IL-2 receptor pathway in MRL/lpr lymphadenopathy: the expanded CD4-8- T cell subset completely lacks functional IL-2 receptors.
Autoimmune MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop a systemic lupus erythematosus-like disease accompanied by a profound lymphadenopathy that consists of CD4-8-B220+ alpha beta T cells. By the use of cross-linking experiments with radiolabeled interleukin-2 (IL-2), these abnormal T cells have been reported to constitutively express the IL-2 receptor beta chain (IL-2R beta), a signal transducing component of IL-2R, in the absence of the alpha chain (IL-2R alpha). To critically reevaluate the role of the IL-2/IL-2R pathway in the pathogenesis of lymphadenopathy we examined expression of the IL-2R alpha and IL-2R beta in MRL/lpr mice by 125I-IL-2 binding analysis and also by flow cytometric analysis using monoclonal antibodies against each component of the receptor. We found that, contrary to the previous report, the CD4-8-B220+ alpha beta T cells in lymph node (LN) of MRL/lpr mice were negative for both IL-2R alpha and IL-2R beta expression. The lpr liver CD4-8-B220+ alpha beta T cells that had been implicated in the genesis of these abnormal LN T cells were also negative for IL-2R beta expression. Therefore, our results indicate that the IL-2/IL-2R system plays little role, if any, in the expansion of abnormal CD4-8-B220+ alpha beta T cells in MRL/lpr mice.
Tanaka
T
T
Department of Immunology, Tokyo Metropolitan Institute of Medical Science, Japan.
Nagasaka
Y
Y
Kitamura
F
F
Kuida
K
K
Suwa
H
H
Miyasaka
M
M
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D005434:Flow Cytometry; D007119:Immunoblastic Lymphadenopathy / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D017493:Leukocyte Common Antigens; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008817:Mice, Mutant Strains; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000954:Antigens, Surface; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens