The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice

MA Maldonado, V Kakkanaiah… - The Journal of …, 1999 - journals.aai.org
MA Maldonado, V Kakkanaiah, GC MacDonald, F Chen, EA Reap, E Balish, WR Farkas…
The Journal of Immunology, 1999journals.aai.org
It has been proposed that the “normal” stimulation of the immune system that occurs from
interactions with environmental stimuli, whether infectious or dietary, is necessary for the
initiation and/or continuation of autoimmunity. We tested this hypothesis by deriving a group
of MRL-lpr mice into a germfree (GF) environment. At 5 mo of age, no differences between
GF and conventional MRL-lpr mice were noted in lymphoproliferation, flow cytometric
analysis of lymph node cells (LN), or histologic analysis of the kidneys. Autoantibody levels …
Abstract
It has been proposed that the “normal” stimulation of the immune system that occurs from interactions with environmental stimuli, whether infectious or dietary, is necessary for the initiation and/or continuation of autoimmunity. We tested this hypothesis by deriving a group of MRL-lpr mice into a germfree (GF) environment. At 5 mo of age, no differences between GF and conventional MRL-lpr mice were noted in lymphoproliferation, flow cytometric analysis of lymph node cells (LN), or histologic analysis of the kidneys. Autoantibody levels were comparably elevated in both groups. A second experiment tested the role of residual environmental stimuli by contrasting GF mice fed either a low mw, ultrafiltered Ag-free (GF-AF) diet or an autoclaved natural ingredient diet (GF-NI). At 4 mo of age, both groups showed extensive lymphoproliferation and aberrant T cell formation, although the GF-AF mice had∼ 50% smaller LNs compared with sex-matched GF-NI controls. Autoantibody formation was present in both groups. Histologic analysis of the kidneys revealed that GF-AF mice had much lower levels of nephritis, while immunofluorescence analysis demonstrated no difference in Ig deposits but did reveal a paucity of C3 deposition in the kidneys of GF-AF mice.
journals.aai.org