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

Abstract

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.

Abnormal Splenic and Thymic IL‐4 and TNF‐α Expression in MRL‐lpr/lpr Mice

“…The administration of IL-2 in MRL-lpr/lpr mice has been shown to ameliorate the autoimmune reaction [24]. Tanaka et al [25] reported that the role of IL-2 and lL-2 receptor in the development of lymphadenopathy of MRL/lpr mice was negligible. The present results were consistent with these reports although there was one MRL--1--1-mouse exhibiting IL-2 transcript in lymph node in our experiments.…”

A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity

“…SCID mice were depleted of natural killer cells by i.p. injection with TM␤-1 rat anti-mouse IL-2R␤ monoclonal antibody (31) (1 mg per animal). After 1 day, 1 ϫ 10 7 human PBMCs were introduced into the peritoneum together with human rIL-4 (0.4 g per animal; PeproTech, Rocky Hill, NJ).…”

Commitment to natural killer cells requires the helix–loop–helix inhibitor Id2

“…CD122͞IL-2R␤ is a component not only of IL-2 but also of IL-15 receptors (40,41). In mice, both the administration of a mAb against CD122 and gene inactivation of CD122 result in severely impaired NK cell development (42,43), demonstrating its essential role for NK cell development. Based on our observation that the CD122 Ϫ subfraction of CD44 ϩ CD25 Ϫ FT cells of wild-type mice contains pT͞NK and pNK (ref.…”