Orally induced peripheral nonresponsiveness is maintained in the absence of functional Th1 or Th2 cells.
Intragastric administration of soluble protein Ags results in peripheral tolerance to the fed Ag. To examine the role of cytokine regulation in the induction of oral tolerance, we fed OVA to mice deficient in Th1 (Stat 4-/-) and Th2 (Stat 6-/-) cells and compared their response to that of normal BALB/c controls. We found that, in spite of these deficiencies, OVA-specific peripheral cell-mediated and humoral nonresponsiveness was maintained in both Stat 4-/- and Stat 6-/- mice. In the mucosa, both Peyer's patch T cell proliferative responses and OVA-specific fecal IgA were reduced in Stat 4-/- and Stat 6-/- mice fed OVA but not in normal BALB/c controls. Mucosal, but not peripheral, nonresponsiveness was abrogated by the inclusion of a neutralizing Ab to TGF-beta in the culture medium. Our results show that, in the periphery, tolerance to oral Ag can be induced in both a Th1- or Th2-deficient environment. In the mucosa, however, the absence of Th1 and Th2 cytokines can markedly affect this response, perhaps by regulation of TGF-beta-secreting cells.
Shi
H N
HN
Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown 02129, USA.
Grusby
M J
MJ
Nagler-Anderson
C
C
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D007108:Immune Tolerance / Q000235:genetics*; D007441:Intubation, Gastrointestinal; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009061:Mouth Mucosa / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics
D004268:DNA-Binding Proteins; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D010047:Ovalbumin