Developmental Changes in Intraepithelial T Lymphocytes and NK Cells in the Small Intestine of Neonatal Rats

Abstract

The main objective of this study was to characterize developmental changes in small intestinal intraepithelial lymphocyte (IEL) subpopulations during the suckling period, thus contributing to the understanding of the development of diffuse gut-associated lymphoid tissue (GALT) and to the identification of early mechanisms that protect the neonate from the first contact with diet and gut microbial antigens. The study was performed by double labeling and flow cytometry in IEL isolated from the proximal and distal small intestine of 1-to 21-d-old Lewis rats. During the suckling period, intraepithelial natural killer (NK) cells changed from a typical systemic phenotype, CD8ϩ, to a specific intestinal phenotype, CD8 -. Analysis of CD8ϩ IEL revealed a progressive increase in the relative number of CD8ϩ IEL co-expressing TCR␣␤, cells associated with acquired immunity, whereas the percentage of CD8ϩ cells expressing the NK receptor, i.e. cells committed to innate immunity, decreased. At weaning, IEL maturity was still not achieved, as revealed by a phenotypic pattern that differed from that of adult rats. Thus, late after weaning, the regulatory CD8ϩCD4ϩ T IEL population appeared and the NK population declined. In summary, the intestinal intraepithelial compartment undergoes changes in its lymphocyte composition associated with the first ingestion of food. These changes are focused on a relatively high proportion of NK cells during the suckling period, and after weaning, an expansion of the regulatory CD8ϩCD4ϩ T cells. Abbreviations DN, double negative (CD8 -CD4 -) DP, double positive (CD8ϩCD4ϩ) dSI, distal small intestine GALT, gut-associated lymphoid tissue IE (L), intraepithelial (lymphocytes) LPL, lamina propria lymphocytes NK, natural killer pSI, proximal small intestine GALT is the largest immunologic organ in the body, with anatomical, phenotypic, and functional features that distinguish it from the systemic immune system and other peripheral lymphoid tissues (1,2). It is also one of the major sites of immunologic challenge. During the early postnatal period, newborns are exposed to a multitude of microbial and nutritional antigens, which challenge the development and complete maturation of both intestinal and systemic immune systems (3,4).GALT contains organized lymphoid structures and diffusely distributed cell populations. Organized GALT comprises Peyer's patches, isolated follicles, and the mesenteric lymph nodes. Diffuse GALT includes IEL and LPL (5). IEL are specialized immune cells whose precise function is not completely understood. They may contribute to cell-mediated mucosal defense with unusual antigen-recognition specificity, surveillance of epithelial cell integrity, and to the pathogenesis of a variety of diseases (6 -8). IEL, like LPL, consist of effector and memory lymphocytes that are generated from antigenstimulated cells in locations such as Peyer's patches. The progeny of these cells migrate systemically and ultimately populate distant mucosal sites (9).The characterization of intestinal IEL h...

Characterization of Clinical and Immune Response in a Rotavirus Diarrhea Model in Suckling Lewis Rats

“…In this sense, in previous studies, we have shown age-related changes in lymphocyte composition and functionality in neonatal rat spleen and mucosal lymphocytes (11,12,22).…”

“…In previous studies, we demonstrated that in early rat life, the intestinal compartment includes a high proportion of NK cells (12,21), which should have an important role in the defense during this stage of development. Current studies also suggest the predominance of IE-NKT during suckling (unpublished observations).…”

“…Intestinal IEL suspensions were isolated and purified from rats during the diarrhea process, on 1 and 3 DPI in L8-HD and LRef groups, as previously described (12). IELs were stained by Fluor chrome-conjugated MAb for flow cytometry analysis as previously described (11).…”

In vitro immunomodulatory activity of Lactobacillus fermentum CECT5716 and Lactobacillus salivarius CECT5713: two probiotic strains isolated from human breast milk

“…In this sense, cytokine production by human NK cells is different at distinct stages of differentiation; for example, TNFa and GM-CSF are produced throughout differentiation, while type 2 cytokines (IL-13 and IL-5) define NK cells at intermediate stages of the process (Loza et al, 2002;Moretta et al, 2008). The enhancement of NK cell maturation by probiotics present in breast milk could be very important during early life, when the proportion of this subset in intestinal sites is higher than in adults (Pé rez-Cano et al, 2005a, 2005b, and because NK cells play a particularly important role in counteracting infections before acquired immunity is fully developed. Such an effect of breast milk probiotics would complement that of other constituents of breast milk, such as lactoferrin (Pé rez-Cano et al, 2007.…”

Reduced Thymic Size and Numbers of Splenic CD4+and CD8+Cells in Artificially Reared Mouse Pups

“…The production of IgA in the suckling mice at 10 days of age may be about 10 times lower than that in adult mice. 18) In a study on rats, the development of IgA bearing lamina propria lymphocytes was delayed until 14 days of age, 19) and the plasma IgA concentration of MR pups at 14 days of age was 2.5 mg/ml, 20) this being approximately 15% of that at 4 wk of age in Sprague-Dawley rats. 21) It is very interesting that the relative thymus weight of the AR-2 pups was respectively significantly larger and smaller than that of the AR-0 and MR pups 10 days after birth (Fig.…”