Accumulation of intestinal intraepithelial lymphocytes in association with lack of polymeric immunoglobulin receptor

Abstract

Immunoglobulin A (IgA) is transported by the polymeric immunoglobulin receptor (pIgR) through epithelial cells of the gut, the airways, the tear and salivary glands, and the lactating mammary gland, and IgA accumulates in serum and the intestinal lamina propria of pIgR‐deficient (pIgR–/–) mice. Intraepithelial lymphocytes (IEL) increased in number and Thy‐1+CD8αβ+TCRαβ+ IEL preferentially expanded in the small intestine (SI) of pIgR–/– mice. Cytotoxic activity of SI‐IEL was comparable in pIgR+/+ and pIgR–/– mice. Accumulation and cytotoxic activity of SI‐IEL was attenuated in germ‐free pIgR–/– mice. Furthermore, Thy‐1+CD8αβ+ IEL did not expand in pIgR–/–TCRβδ–/– mice compared with TCRβδ–/– mice, and SI‐IEL from pIgR–/–TCRβδ–/– mice as well as TCRβδ–/– mice expressed perforin and granzyme B mRNA and serine esterase. The proliferative status of SI‐IEL from pIgR+/+ and pIgR–/– mice was similar, but adoptive transfer experiment showed that SI‐IEL from pIgR–/– mice might have a stronger tendency to migrate into the intestinal epithelia than those from pIgR+/+ mice. These results demonstrate that the accumulation of Thy‐1+CD8αβ+TCRαβ+ IEL in pIgR–/– mice triggered by intestinal microorganisms needed the expression of functional TCR and might be caused by lymphocyte migration into the intestinal epithelia.

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

“…18 Therefore, we consider that pIgR À/À mice can be used to reveal the abnormalities caused by the lack of secretory antibody. As reported previously, 17 there were more ab-IELs in the SI of adult pIgR À/À mice with an age of 11-12 weeks compared with age-matched pIgR +/+ mice (Fig. 1a).…”

“…As reported previously, 17 there were more ab-IELs in the SI of adult pIgR À/À mice with an age of 11-12 weeks compared with age-matched pIgR +/+ mice (Fig. 1a).…”

“…Our previous report revealed that CD8ab + T-cell receptor (TCR)-ab + intraepithelial lymphocytes (CD8ab + ab-IELs) accumulate in the small intestine (SI) of pIgR À/À mice in response to commensal bacteria. 17 This study shows that enhanced differentiation and activation of CD8ab + ab-IELs occur in the SI of pIgR À/À mice, subsequently resulting in the abnormalities of epithelial integrity. These results demonstrate the importance of sIgA in the maintenance of gut homeostasis.…”

“…The SI-IELs were prepared as described elsewhere. 17 Briefly, fragments of SI tissues approximately 1-2 cm in length were vigorously shaken in 5% fetal calf serum/25 mM HEPES/RPMI-1640 for 45 min to separate the cells from the intestinal wall. Cells were recovered by centrifugation in 30% Percoll solution (GE Healthcare Life Sciences Japan, Tokyo, Japan).…”

Polymeric Immunoglobulin Receptor in Intestinal Immune Defense against the Lumen-Dwelling Protozoan ParasiteGiardia

“…These mice are generally healthy, although they show increased levels of circulating IgA, as well as IgG, and increased immune reactivity against Ags from commensal bacteria (9), suggesting that pIgR-dependent IgA excretion into the intestinal lumen is important for preventing immune activation by enteric commensals and food Ags. The mice also exhibit modest increases in intestinal IgA-secreting cells and intraepithelial lymphocytes (11,12), although the functional significance of these observations is unclear. Moreover, deficiency in pIgR interfered with normal immune protection against infection with the respiratory pathogens Streptococcus pneumoniae, Mycobacterium tuberculosis, and the influenza virus in the lungs and nasal cavity in mice (13)(14)(15), indicating a role of the receptor in immune defense against respiratory pathogens.…”