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      Characterization of the diffuse mucosal associated lymphoid tissue of feline small intestine

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          Abstract

          Characterization of the feline intestinal mucosal associated lymphoid tissue (MALT) will facilitate investigation of intestinal disease in the cat and promote the cat as an animal model for a range of human diseases which involve the intestinal lymphoid tissue. This includes inflammatory bowel disease, viral and non-viral associated intestinal lymphomas and immunodeficiency associated syndromes. Morphologic and phenotypic characterization of the normal small intestinal diffuse MALT in 22 SPF cats was performed using flow cytometry and cytology on isolated intestinal leukocytes from the intra-epithelial and lamina proprial compartments, as well as immunohistology on tissues from the feline duodenum, jejunum and ileum. The intra-epithelial compartment (IEC) was dominated by lymphocytes (>85%) which frequently contained intracytoplasmic granules. The most striking findings in the IEC were the elevated percentages of CD8α+ lymphocytes (40%), presumed to express CD8αα chains, and CD4−/CD8− (double negative) lymphocytes (44%), and the consistent presence of a minor subpopulation of CD3+/CD11d+ IELs (6%). Small percentages of CD4+ lymphocytes (10%) were observed such that the IEL CD4:CD8 ratio (0.25) was low. The LPC also contained a majority of T cells and few plasma cells. However, this compartment had reduced percentages of CD8α+ lymphocytes (28%) and increased percentages of CD4+ lymphocytes (27%) relative to the IEC. However, the LPL CD4:CD8 ratio (1.0) remained low compared with the ratio in peripheral blood. In feline MALT, MHC class II expression was lower than in other peripheral lymphoid compartments. The results of this study provide important reference values for future investigations involving feline intestinal lymphocytes and demonstrates that the leukocyte distribution and phenotypic characteristics of the feline diffuse MALT appear largely similar to the murine, rat and human counterparts.

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          Most cited references48

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          The anatomical basis of intestinal immunity.

          The lymphoid tissues associated with the intestine are exposed continuously to antigen and are the largest part of the immune system. Many lymphocytes are found in organised tissues such as the Peyer's patches and mesenteric lymph nodes, as well as scattered throughout the lamina propria and epithelium of the mucosa itself. These lymphocyte populations have several unusual characteristics and the intestinal immune system is functionally and anatomically distinct from other, peripheral compartments of the immune system. This review explores the anatomical and molecular basis of these differences, with particular emphasis on the factors which determine how the intestinal lymphoid tissues discriminate between harmful pathogens and antigens which are beneficial, such as food proteins or commensal bacteria. These latter antigens normally provoke immunological tolerance, and inappropriate responses to them are responsible for immunopathologies such as food hypersensitivity and inflammatory bowel disease. We describe how interactions between local immune cells, epithelial tissues and antigen-presenting cells may be critical for the induction of tolerance and the expression of active mucosal immunity. In addition, the possibility that the intestine may act as an extrathymic site for T-cell differentiation is discussed. Finally, we propose that, under physiological conditions, immune responses to food antigens and commensal bacteria are prevented by common regulatory mechanisms, in which transforming growth factor beta plays a critical role.
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            Subsets of CD3+ (T cell receptor alpha/beta or gamma/delta) and CD3- lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood.

            Intestinal intraepithelial lymphocytes (IEL) were studied, after isolation in humans, for their surface antigens with a large variety of monoclonal antibodies. They show peculiar characteristics when compared with peripheral blood lymphocytes and intestinal lamina propria lymphocytes. Although a majority of human intraepithelial lymphocytes (IEL) express an alpha/beta type of T cell receptor (TcR), 13% express a gamma/delta TcR, a percentage which was significantly higher than that found in blood and in lamina propria. In contrast to observations in mice, there was no evidence that normal human TcR gamma/delta+ intestinal IEL might use preferential variable segments of gamma genes. About 10% of human intestinal IEL expressed the alpha chain but not the beta chain of CD8, thus resembling a subset of CD8 alpha+beta- IEL, which was recently described in mice and found to be of thymoindependent origin. In addition, 10% of human IEL had a unique phenotype of immature T cells, as they bore only CD7, but no other T cell or natural killer cell markers. Finally, even the major population of IEL which expressed the usual markers of the T cell lineage (CD3, TcR alpha/beta, CD2, CD4 or CD8 alpha/beta) differed from peripheral blood T lymphocytes by their peculiar expression of surface antigens associated with activation. Indeed, 80% of IEL were CD45R0+, CD45A-, but co-expression of CD11a, CD29 and LFA-3 was inconstant. In addition, 90% of IEL expressed HML-1.
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              The B-cell surface protein CD72/Lyb-2 is the ligand for CD5.

              The glycoprotein CD5 is expressed on the surface membrane of all mature T cells and a small proportion of B lymphocytes. Its exact role in immune interactions is still unknown. Studies indicate that CD5 functions both in mice and humans as a receptor, delivering co-stimulatory signals to T cells in a manner similar to CD2 (ref. 11) and CD28 (ref. 12). Anti-CD5 antibodies stimulate both T-cell proliferation mediated by CD3 in association with the T-cell receptor and secretion of interleukin-2 and expression of its receptor, as well as inducing an increase in intracellular Ca2+ concentration (refs 5-10). To identify the ligand for CD5 we purified the human CD5 protein, labelled it with biotin and used it as a probe. Here we report that CD5 specifically interacts with the cell-surface protein CD72 exclusive to B cells. This interaction is blocked by anti-CD72 antibodies, but not by any other anti-B-cell antibodies. Moreover, non-B cells (mouse L-cell fibroblasts and human Jurkat T cells) expressing a transfected human CD72 complementary DNA could bind to the CD5-biotin conjugate. The results demonstrate that the B-cell surface protein CD72 (Lyb-2 in mice) is the ligand for CD5.
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                Author and article information

                Contributors
                Journal
                Vet Immunol Immunopathol
                Vet. Immunol. Immunopathol
                Veterinary Immunology and Immunopathology
                Elsevier Science B.V.
                0165-2427
                1873-2534
                7 July 2000
                30 June 2000
                7 July 2000
                : 75
                : 1
                : 27-42
                Affiliations
                [a ]Istituto di Anatomia Patologica Veterinaria e Patologia Aviare, Facoltaı́ di Medicina Veterinaria, Via Celoria n. 10, 20133 Milan, Italy
                [b ]Department of Veterinary Pathology, Immunology and Microbiology, School of Veterinary Medicine, University of California at Davis, Davis, CA 95616, USA
                Author notes
                [* ]Corresponding author. Tel.: +1-530-752-6611; fax: +1-530-752-3349 pfmoore@ 123456ucdavis.edu
                Article
                S0165-2427(00)00181-1
                10.1016/S0165-2427(00)00181-1
                7119714
                10889297
                a4fc0b63-a9f3-4328-a618-415f87eb6edd
                Copyright © 2000 Elsevier Science B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 10 December 1999
                : 24 February 2000
                : 6 March 2000
                Categories
                Article

                Veterinary medicine
                feline,small intestine,mucosal,lymphocyte,malt,phenotype
                Veterinary medicine
                feline, small intestine, mucosal, lymphocyte, malt, phenotype

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