Mesenteric lymph nodes are critical for the induction of high‐dose oral tolerance in the absence of Peyer's patches

TW Spahn, HL Weiner, PD Rennert… - European journal of …, 2002 - Wiley Online Library
TW Spahn, HL Weiner, PD Rennert, N Lügering, A Fontana, W Domschke, T Kucharzik
European journal of immunology, 2002Wiley Online Library
We have previously demonstrated the loss of oral tolerance (OT) in lymphotoxinα−/−(LTα−/−)
and TNFα/lymphotoxinα deficient (TNFα/LTα−/−) mice which have defective Peyer's patches
(PP) and lymph node (LN) development. We have now studied OT in BALB/c mice with
differential defects of the gut‐associated lymphoid tissue (GALT) caused by inhibition of
LTβR signaling during fetal development. Treatment of pregnant mice with LTβR‐IgG
(LTβRIgG) and TNFR I (55)‐IgG (TNFR55IgG) abrogates the formation of PP (LTβRIgG) or of …
Abstract
We have previously demonstrated the loss of oral tolerance (OT) in lymphotoxinα − / − (LTα − / −) and TNFα / lymphotoxinα deficient (TNFα / LTα − / −) mice which have defective Peyer's patches (PP) and lymph node (LN) development. We have now studied OT in BALB / c mice with differential defects of the gut‐associated lymphoid tissue (GALT) caused by inhibition of LTβR signaling during fetal development. Treatment of pregnant mice with LTβR‐IgG (LTβRIgG) and TNFR I(55)‐IgG (TNFR55IgG) abrogates the formation of PP (LTβRIgG) or of PP and mesenteric LN (MLN) (LTβRIgG / TNFRIgG) without genetically deleting the respective cytokine pathways. OT was readily induced in mice without PP but retaining MLN (PP null / LN +). In contrast, OTcould not be induced in mice lacking both MLN and PP (PP null / MLN null) as shown by the inability of these mice to suppress IFN‐γ secretion or DTH reactions. We next assessed OT in 129 × B6 LTα − / − mice with and without MLN. Timed treatment of pregnant LTα − / − mice with an agonist anti‐LTβR mAb induces formation of MLN but not of PP in LTα − / − mice. LN + LTα −/ − mice developed OT while LN LTα − / − mice were resistant to OT induction. Taken collectively, the data show that in the presence of MLN PP are not required for OT induction and that the presence of MLN is sufficient for OT induction in the LTα − / − model.
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