Enhanced differentiation of intraepithelial lymphocytes in the intestine of polymeric immunoglobulin receptor-deficient mice.

To clarify the effect of secretory IgA (s IgA) deficiency on gut homeostasis, we examined intraepithelial lymphocytes ( IELs) in the small intestine ( SI) of polymeric immunoglobulin receptor-deficient ( pIgR^−/−) mice. The p IgR^−/− mice exhibited the accumulation of CD8 αβ⁺ T-cell receptor ( TCR)- αβ⁺ IELs ( CD8 αβ⁺ αβ- IELs) after weaning, but no increase of CD8 αβ⁺ γδ- IELs was detected in pIgR^−/− TCR- β^−/− mice compared with pIgR^+/+ TCR- β^−/− mice. When 5-bromo-2′-deoxyuridine (BrdU) was given for 14 days, the proportion of BrdU-labelled cells in SI- IELs was not different between pIgR^+/+ mice and pIgR^−/− mice. However, the proportion of BrdU-labelled CD8 αβ⁺- IELs became higher in pIgR^−/− mice than pIgR^+/+ mice 10 days after discontinuing BrdU-labelling. Intravenously transferred splenic T cells migrated into the intraepithelial compartments of pIgR^+/+ TCR- β^−/− mice and pIgR^−/− TCR- β^−/− mice to a similar extent. In contrast, in the case of injection of immature bone marrow cells, CD8 αβ⁺ αβ- IELs increased much more in the SI of pIgR^−/− TCR- β^−/− mice than pIgR^+/+ TCR- β^−/− mice 8 weeks after the transfer. αβ- IELs from pIgR^−/− mice could produce more interferon- γ and interleukin-17 than those of pIgR^+/+ mice, and intestinal permeability tended to increase in the SI of pIgR^−/− mice with aging. Taken together, these results indicate that activated CD8 αβ⁺ αβ- IELs preferentially accumulate in pIgR^−/− mice through the enhanced differentiation of immature haematopoietic precursor cells, which may subsequently result in the disruption of epithelial integrity. [ABSTRACT FROM AUTHOR]