The influence of gut function on lymphoid cell populations in the intestinal mucosa of lambs.

The number and type of lymphoid cells in the intestinal mucosa of lambs change during the first weeks after birth. The influence of gut function on these changes was examined by comparing the evolution of lymphoid cell populations in normal ileum with that in lengths of ileum which had been isolated surgically from the functional intestinal tract of the lamb before birth. The isolated lengths of ileum had a normal blood and nerve supply and they remained healthy throughout a period of at least 2 years, although they did not have a normal histological development. In comparison with normal ileum, the villi of the isolated ileal segments were much smaller and there were many fewer intraepithelial lymphocytes; the lamina propria had significantly fewer lymphocytes than the functional ileum and only a few plasma cells. When isolated ileal segments were reconnected into the intestinal tract after having been isolated from it for 1-3 months, the histology of the mucosa reverted to that of the normal gut, with the same number and types of lymphoid cells. Radiolabelled lymphoblasts collected from intestinal lymph and injected intravenously accumulated to only a small extent in isolated segments of ileum compared with either the normal or the reconnected segments of ileum. This suggested that the paucity of lymphocytes in the mucosa of the isolated segments was due to a reduced extravasation of these cells there. The influence which the gut contents exert on the lymphoid cell population in the mucosa is probably associated with antigenic stimulation but may also be related to other factors concerned in the normal digestive functions of the gut.     

Ileal and jejunal Peyer’s patches play distinct roles in mucosal immunity of sheep

The majority of pathogens enter the body through mucosal surfaces and it is now evident that mucosal immunity can provide effective disease protection. However, the induction of mucosal immunity will require efficient targeting of mucosal vaccines to appropriate mucosa-associated lymphoid tissue. An animal model, based upon the surgical preparation of sterile intestinal 'loops' (blind-ended segments of intestine), was developed to evaluate mucosal and systemic immune responses to enteric vaccines in ruminants. The effectiveness of end-to-end intestinal anastomoses was evaluated and fetal surgery did not disrupt normal intestinal function in lambs up to 6-7 months after birth. The immunological competence of Peyer's patches (PP) within the intestinal 'loops' was evaluated with a human adenovirus 5 vector expressing the gD gene of bovine herpesvirus-1. This vaccine vector induced both mucosal and systemic immune responses when injected into intestinal 'loops' of 5-6-week-old lambs. Antibodies to the gD protein were detected in the lumen of intestinal 'loops' and serum and PP lymphocytes proliferated in response to gD protein. The immune competence of ileal and jejunal PP was compared and these analyses confirmed that jejunal PP are an efficient site for the induction of mucosal immune responses. This was confirmed by the presence of gD-specific antibody-secreting cells in jejunal but not ileal PP. Systemic but not mucosal immune responses were detected when the vaccine vector was delivered to the ileal PP. In conclusion, this model provided an effective means to evaluate the immunogenicity of potential oral vaccines and to assess the immunological competence of ileal and jejunal Peyer's patches.     

Postnatal development and lymphocyte production of jejunal and ileal Peyer's patches in normal and gnotobiotic pigs.

The development of the number, size, structure and proliferative capacity of Peyer's patches (PP) in the jejunum and ileum has been studied during the early postnatal period of conventional and germ-free pigs. A mean of 15 discrete PP in the jejunum and upper ileum (jejPP) were counted at birth, and the number increased only gradually. A continuous PP is located in the terminal ileum (ileal PP). The length of both jejPP and ileal PP increased with age due to the increase in follicle size and in the number of follicles in the ileal PP. In older pigs, only the ileal PP regressed to small scattered follicles. In germ-free piglets at 39 and 59 days of age, longer PP were found than in normal new-born piglets, but they were significantly shorter than in age-matched controls. Lymphocyte production was studied by the metaphase-arrest technique using vincristine. Lymphocyte production in follicles increased dramatically with age, while in other compartments, such as the inter-follicular and dome area, a low age-independent production of lymphocytes was found. There were no differences in lymphocytopoiesis between jejPP and ileal PP. The present data show major differences in the development, structure and function of PP in pigs in comparison to other species. These species-specific aspects are important for future studies on the immunological function of PP.     

The evolution and involution of Peyer's patches in fetal and postnatal sheep

The Peyer's patches (PP) of sheep have a number of important anatomical features and functional characteristics which are similar to tissues that have been classified as primary lymphoid organs. The prenatal maturation of PP occurs in the absence of any antigenic stimulus as immunogenic molecules are not normally encountered by the sheep fetus. Primordial PP were first detected in the small intestine of fetal sheep at about 60-days gestation; lymphoid follicles were present by 75-days gestation and vigorous lymphopoiesis was occurring in these follicles by 100 days. From 120-days gestation until birth, at about 150 days, the PP follicles were histologically mature and they had the greatest density of proliferating lymphoid cells found anywhere in the body. The total number of PP and their constituent follicles had developed before birth when there were 25-40 discrete PP in the jejunum and proximal ileum and one single continuous PP in the terminal ileum. There was no evidence of any change in the rate of growth of the PP follicles at birth which could be related to the advent of the first antigens in the gut. The total weight of PP tissue was greater than any other single lymphoid tissue by about 6 weeks after birth weighing around 120 g or about 1.2% of the body weight; about 50-60 g of the PP tissue was calculated to be lymphoid tissue. At this time the ileocecal PP (IPP) extended 2.5 m along the terminal ileum and accounted for about 90% of the total mass of PP. From about 12 weeks after birth the IPP began to involute and only a few PP follicles remained in this region of the intestine by 18 months of age. Follicles in PP in other parts of the small intestine remained and continued to produce lymphocytes throughout the life of the animal. PP contain a number of anatomically and functionally distinct lymphoid compartments that could play different roles in the body's immune defense. Explicit in most theories on the function of PP is the notion that antigenic stimulation is the cause of the lymphopoiesis in the follicles; our results do not support this view. Instead they suggest that the follicles in the PP of sheep may play a role similar to that played by the bursa of Fabricius in birds.     

Characterization of B-cell phenotypic changes during ileal and jejunal Peyer's patch development in sheep.

Changes in B-cell phenotype during development of ileal and jejunal Peyer's patches (PP) of sheep were investigated using flow cytometry and immunoperoxidase-stained cryosections. On Day 104 of gestation (term at 150 days) B-cell clusters were identified in the lamina propria of the ileum. These clusters were composed of cells that expressed surface IgM (sIgM), lambda or kappa light chain, and BAQ44A, a B-cell differentiation molecule. No cells in the clusters stained for terminal deoxynucleotide transferase. On Day 132 gestation, a change was evident in the phenotype of ileal PP B cells. Most B cells expressed a reduced level of sIgM and 20% were BAQ44A-. The B cells in the dome region were BAQ44A+ but few BAQ44A+ cells were present in the follicles. At 6-8 weeks of age BAQ44A+ cells were restricted to the dome region of the ileal PP; flow cytometric analysis confirmed that 25% of B cells isolated from the dome/follicle complex were BAQ44A+. Thus, the primordial PP was populated with B cells that were phenotypically similar to circulating B cells (sIgMhigh, BAQ44A+). After 132 days gestation, the predominant B-cell phenotype in the ileal PP changed to sIgMlow and BAQ44A-. This phenotypic change could be the result of either early immigrant B-cell differentiation or subsequent colonization by sIgMlow BAQ44A- B cells. The phenotypic changes of ileal PP follicular B cells were not complete until after birth and different phenotypic changes were observed in follicles of the jejunal PP of young lambs.     

A comparative study of gut-associated lymphoid tissue in calf and chicken

The calf contains two types of Peyer's patches (PPs): jejunal and ileal. The ileal PP has been thought to be equivalent to the bursa of Fabricius (BF) as a central lymphoid organ. The morphologies of ileal and jejunal PPs in the calf were compared with those of the BF and the caecal tonsil (CT) in the chicken. Immunoglobulin G-positive (IgG(+)) cells appear in the follicles of them all and exhibited a dendritic appearance after birth. We investigated whether the IgG in these follicles was produced in situ. IgG-producing cells were detected in the follicular medullas of the jejunal PP and the CT, but not in those of the ileal PP and the BF. CD4(+) cells were distributed in the follicular medullas of the jejunal PP and the CT, but not in those of the ileal PP and the BF. The data suggest that Ig class switching occurs in both jejunal PP follicles and CT follicles, but does not occur in either the ileal PP follicles or the bursal follicles. Because CD4(+) T cells would be prerequisite for Ig class switching in these follicles, IgG(+) cells of the follicular medullas in the ileal PP and the BF would trap immune complexes from the gut lumen. The primary B-cell repertoire might be selected by gut-derived antigens in the ileal PP and the BF before seeding the periphery.     

Histological studies on the ontogeny of bovine gut-associated lymphoid tissue: appearance of T cells and development of IgG+ and IgA+ cells in lymphoid follicles

The development and distribution of lymphocyte subsets in bovine gut-associated lymphoid tissues (ileal and jejunal Peyer's patches (PP)) were examined. Before birth, the composition of lymphocyte subsets in both PP follicles did not differ except for the dimensions of the interfollicular area and the dome region. Many IgM+ cells were observed in these follicles, but very few CD3+, IgG+, and IgA+ cells could be found. At neonatal period, the IgG+ cells, which did not produce IgG mRNA, were dominant within both PP follicles. From 1 month after birth, many CD3+ cells, IgG mRNA expression, and IgA mRNA expression were detected within the jejunal PP follicles, but very few were in the ileal PP follicles. These data suggest that the characteristics of the jejunal PP follicles metamorphose into secondary lymphoid tissue such as germinal centers at around 1 month after birth, whereas the characteristics of ileal PP follicles were distinct from those of germinal centers.     

A comparative study of gut‐associated lymphoid tissue in calf and chicken

The calf contains two types of Peyer's patches (PPs): jejunal and ileal. The ileal PP has been thought to be equivalent to the bursa of Fabricius (BF) as a central lymphoid organ. The morphologies of ileal and jejunal PPs in the calf were compared with those of the BF and the caecal tonsil (CT) in the chicken. Immunoglobulin G–positive (IgG⁺) cells appear in the follicles of them all and exhibited a dendritic appearance after birth. We investigated whether the IgG in these follicles was produced in situ. IgG‐producing cells were detected in the follicular medullas of the jejunal PP and the CT, but not in those of the ileal PP and the BF. CD4⁺ cells were distributed in the follicular medullas of the jejunal PP and the CT, but not in those of the ileal PP and the BF. The data suggest that Ig class switching occurs in both jejunal PP follicles and CT follicles, but does not occur in either the ileal PP follicles or the bursal follicles. Because CD4⁺ T cells would be prerequisite for Ig class switching in these follicles, IgG⁺ cells of the follicular medullas in the ileal PP and the BF would trap immune complexes from the gut lumen. The primary B‐cell repertoire might be selected by gut‐derived antigens in the ileal PP and the BF before seeding the periphery. Anat Rec 266:207–217, 2002. © 2002 Wiley‐Liss, Inc.     

Lymphoid follicles of different phenotype appear in ileum during involution of the sheep ileal Peyer's patch

The ileal Peyer's patch (IPP) of young sheep is a site of diversification of the primary antibody repertoire and where involution takes place at young age. Tissue samples from the ileum were collected in 134 animals aged from 1 month to 6 years, and IPP follicle phenotypes were characterised. We describe a new type of ileal lymphoid follicles that became relatively more frequent during involution, and had numerous intrafollicular T-cells and BAQ44A+ B-cells and large interfollicular T-cell areas. As opposed to classical IPP follicles in which the BAQ44A+ cells were confined to the narrow follicle-neck region, the novel atypical ileal lymphoid follicle had these cells distributed throughout the follicle. The relative distribution of cell types in the typical IPP follicle remained fairly constant during involution. Many animals older than 9 months (64/92) still had had typical IPP follicles and even sheep 4 years and older (5/9) had IPP-type follicles.     

Mitotic rate maturation in the Peyer's patches of fetal sheep and in the bursa of Fabricius of the chick embryo

The metaphase arrest technique was used to quantitate the mitotic rate in sheep Peyer's patches (PP) and in the chicken bursa of Fabricius. It was shown that the mitotic rate in these tissues was the same whether or not the animal had been exposed to extrinsic antigen. The mitotic rate was calculated from the rate of accumulation of metaphase cells in tissue sections taken up to 4 h after i.v. vincristine. The follicular B cells in PP of fetal sheep at 3-5 days before birth, and in the bursas of chick embryos 2-3 days before hatching, none of which had experienced extrinsic antigen, entered mitosis at a rate of 5.2%/h and 7.5%/h, respectively. A similar analysis was done on animals at approximately 6 weeks of age, at which stage the PP and bursa had received chronic exposure to antigen from the gut. The mitotic rates were not significantly different from those in fetuses, i.e., 5.4%/h for PP and 6.0%/h for the bursa. In the follicles of both young lambs and juvenile chickens, the mitotic rate was 2-3 times greater in the outer, or cortical zone, than in the inner, or medullary zone. In a similar study of the thymus, no significant differences were found between the mitotic rates in fetal sheep and young lambs. The mitotic rate for the thymus was 15-20-fold less than for the PP. It is proposed that sheep PP, the chicken bursa and the thymus have in common the important characteristic of establishing a maximal rate of lymphocyte division prior to being exposed to antigen.     

Unique Microanatomy of Ileal Peyer's Patches of the One Humped Camel (Camelus dromedarius) is not Age‐Dependent

The Peyer's patches (PP) have been intensely investigated in several species because this is an important entry site for antigens and infectious agents. There are many PP in the jejunum, and in some species such as ruminants, carnivores, and omnivores, a different continuous PP is found in the terminal ileum. This PP disappears with age in these species studied. So far the ileal PP (IPP) has only been examined in the camel by light microscopy. Therefore, the localization of ileal Peyer's patches in the dromedary camel at different ages, as well as the histology and ultrastructures were now investigated. The IPP were characteristically seen as dark rose‐colored isolated structures in the shape of a cup, arranged in three irregular rows. The central row was antimesenteric. Each patch was formed by several mainly elongated dome regions flanked by intestinal villi. In cross‐sections these domes appeared as short, wide villi. The domes were formed from lymphoid follicles covered with a typical dome‐associated epithelium of enterocytes and M cells without any goblet cells. The M cells showed variable appearance depending on the functional status. The lymphoid follicles expressed clear germinal centers. High endothelial venules were localized in the interfollicular region. In contrast to other species the IPP were still present with a comparable macroscopic and histological structure in camels of 25 years of age. Anat Rec, 291:1023–1028, 2008. © 2008 Wiley‐Liss, Inc.     

Lymphocyte depletion in ileal Peyer's patch follicles in lambs infected with Eimeria ovinoidalis.

A total of 14 lambs were experimentally infected with Eimeria ovinoidalis in two separate experiments in two consecutive years. Nine lambs served as uninoculated controls. Material was collected from the ileum 2 weeks after infection in eight lambs and 3 weeks after infection in six lambs. Lambs examined 2 weeks after infection had normal follicles. After three weeks, the follicle-associated epithelium covering the lymphoid follicles of the ileal Peyer's patches showed fusions with adjacent absorptive epithelium, focal hyperplasia, and occasionally necrosis. Macrogametes, microgamonts, and oocysts were often found in the follicle-associated epithelium and the dome region. Various degrees of lymphocyte depletion were present in the ileal lymphoid follicles in all six infected lambs 3 weeks after infection, and four lambs had decreased follicle size. Reduced staining for leukocyte common antigen (CD45), B-cell markers, and the proliferation marker Ki-67 was present in these lambs. Application of the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling method for apoptotic cells revealed decreased staining in the ileal lymphoid follicles 3 weeks after infection. A marker of follicular dendritic cells, 5'- nucleotidase, showed increased reactivity, probably due to condensation of reticular cells following loss of follicle lymphocytes. Reduced staining for carbonic anhydrase in the follicle-associated epithelium and the domes was present in all six lambs examined 3 weeks after infection, indicating decreased production of carbonic anhydrase-reactive 50-nm particles and a decreased lymphoproliferative stimulus. In conclusion, the present study shows that severe E. ovinoidalis infection in lambs causes lesions of the follicle-associated epithelium and may result in lymphocyte depletion and atrophy of the ileal Peyer's patch follicles.     

Lymphocyte Depletion in Ileal Peyer’s Patch Follicles in Lambs Infected with Eimeria ovinoidalis

A total of 14 lambs were experimentally infected with Eimeria ovinoidalis in two separate experiments in two consecutive years. Nine lambs served as uninoculated controls. Material was collected from the ileum 2 weeks after infection in eight lambs and 3 weeks after infection in six lambs. Lambs examined 2 weeks after infection had normal follicles. After three weeks, the follicle-associated epithelium covering the lymphoid follicles of the ileal Peyer’s patches showed fusions with adjacent absorptive epithelium, focal hyperplasia, and occasionally necrosis. Macrogametes, microgamonts, and oocysts were often found in the follicle-associated epithelium and the dome region. Various degrees of lymphocyte depletion were present in the ileal lymphoid follicles in all six infected lambs 3 weeks after infection, and four lambs had decreased follicle size. Reduced staining for leukocyte common antigen (CD45), B-cell markers, and the proliferation marker Ki-67 was present in these lambs. Application of the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling method for apoptotic cells revealed decreased staining in the ileal lymphoid follicles 3 weeks after infection. A marker of follicular dendritic cells, 5′- nucleotidase, showed increased reactivity, probably due to condensation of reticular cells following loss of follicle lymphocytes. Reduced staining for carbonic anhydrase in the follicle-associated epithelium and the domes was present in all six lambs examined 3 weeks after infection, indicating decreased production of carbonic anhydrase-reactive 50-nm particles and a decreased lymphoproliferative stimulus. In conclusion, the present study shows that severe E. ovinoidalis infection in lambs causes lesions of the follicle-associated epithelium and may result in lymphocyte depletion and atrophy of the ileal Peyer’s patch follicles.     

Lesions in subclinical paratuberculosis of goats are associated with persistent gut-associated lymphoid tissue

The organized gut-associated lymphoid tissue (the Peyer's patches [PPs] of domestic ruminants) is an important site of lesions caused by Mycobacterium avium subsp. paratuberculosis. To investigate the association between PP morphology and the lesions of paratuberculosis in goats, two experiments were performed. Five healthy kids aged 4-5 weeks were examined and the morphology of organized lymphoid tissue in the small intestine was described. Morphological similarities were observed between the ileocaecal-valve PP (ICVPP) and the jejunal PPs (JPPs), with pear-shaped follicles, large submucosal interfollicular T-cell areas, and many intraepithelial leucocytes in the follicle-associated epithelium. The ileal PP (IPP) consisted of elongated follicles, small T-cell areas and few intraepithelial leucocytes. The association between these three locations of PPs and lesions of paratuberculosis was then studied in seven goats inoculated with M. a. paratuberculosis at 5-8 weeks of age and killed 2 years later, while in the subclinical phase of infection. Gross lesions were recorded in five animals and microscopic lesions were observed in the intestine and mesenteric lymph nodes of six animals. The lesions in the small intestine were mainly located in the PPs of the mid-jejunum (JPPs) and ICVPP. Lesions were not present in the intestinal segments that had contained IPP, which had undergone involution during the first 12-18 months of life. These observations indicate that the persistent organized lymphoid tissue in the JPPs and ICVPP, but not the involuted IPP, sustains the development of granulomatous inflammation due to paratuberculosis during the subclinical phase of infection.     

Two types of sheep Peyer's patches: location along gut does not influence involution.

In sheep, and some other species, there is evidence of two types of Peyer's patches (PPs), the ileal PP, which extends 150 cm along the terminal ileum, and the jejunal PPs distributed throughout the rest of the small intestine. The two types differ significantly in their histology, ontogeny and the extent of lymphocyte traffic. Another intriguing difference is that the ileal PP involutes about the time of puberty whereas the jejunal PPs function throughout life. This study shows that the differences in PP lifespan is not related to their specific location in the small intestine. Surgery was done at 1-2 months of age to transpose lengths of ileal PP into the jejunum, also, PP-containing lengths of jejunum were transposed into the midst of the ileal PP. Examination at age 12-16 months showed that ileal PP transposed into jejunum had involuted at the same rate as normally sited ileal PP. Also, jejunal PPs transposed into the ileum had not involuted unlike the surrounding ileal PP. It was concluded that the difference in lifespan of the two PPs were not related to the local microenvironment created by gut function, but may be inherent to the PP itself.     

Differential peripheral expansion and in vivo antigen reactivity of alpha/beta and gamma/delta T cells emigrating from the early fetal lamb thymus

The concentrations of different lymphocyte subsets in the blood of lambs which had been thymectomized (Tx) in utero between days 67-75 of fetal gestation were measured at birth and at various intervals during the first year of life. Compared to thymus-intact (Ti) controls, Tx lambs were severely depleted of both alpha/beta and gamma/delta T cells at birth (less than 10% of control levels). The majority of the residual alpha/beta T cells present in Tx lambs at birth were CD4+CD8-. As the Tx lambs aged, the concentration of alpha/beta T cells in blood increased steadily to reach levels around 50% of control values. In contrast, the circulating gamma/delta T cells did not expand in Tx animals and remained barely detectable throughout the observation period, although these cells accounted for 30%-60% of the T cells in the blood of Ti lambs. The expansion of alpha/beta but not gamma/delta T cells was also reflected in changes in the cellular composition of solid lymphoid organs in Tx lambs. B cell numbers were similar in both groups at birth but Tx lambs were persistently B lymphopenic from 3 weeks of age onwards. The alpha/beta T cells that had expanded in Tx lambs responded to stimulation with bacterial antigens in a way that was qualitatively similar to the response in Ti lambs. By contrast, the few gamma/delta T cells in Tx lambs responded abnormally. Our results show that although sheep alpha/beta and gamma/delta T cells are equally thymus dependent during ontogeny, the early fetal thymic emigrants which establish the two T cell lineages in the periphery have strikingly different antigen reactivities and capacities for self-renewal and expansion.     

The development of gut associated lymphoid tissue in the terminal ileum of fetal human intestine.

Lymphoid tissue in formalin fixed and snap frozen human fetal ileum has been studied using immunohistochemistry. At 11 weeks gestation clusters of cells expressing CD4 (leu-3a positive) are present in fetal ileum but these do not express CD3 (UCHT1 negative) and are probably macrophages. Aggregates of lymphoid tissue are apparent from 14 weeks gestation which contain T cells of helper/inducer and suppressor/cytotoxic phenotype. Both B and T cells are present at 16 weeks but with no cellular zonation. By 19 weeks, distinct follicles of B cells are present surrounded by T cells of helper/inducer and suppressor/cytotoxic phenotype. Follicular dendritic cells are also present within the B cell areas. The B cells at this age express surface IgM and IgD, C3b- and C3d-receptors. They also express the antigen CD5 which has been shown by others to be present on some fetal B cells but which is almost exclusively associated with T cells in the adult. HLA-D region antigens are present on apparently all of the cells within the fetal lymphoid follicles. The antigen on activated B cells, CD23 (recognized by MHM6), was present on some cells scattered within the B cell follicle. This is indicative of antigen independent B cell proliferation.     

Phenotypic characterisation of intestinal dendritic cells in sheep

The present study was undertaken to identify dendritic cells (DCs) in the ileum and rectum of lambs and adult sheep. The distribution of these cells in four different intestinal compartments, i.e. lamina propria, lymphoid follicles, domes and interfollicular areas was assessed, and the presence of these cells in lambs and adult sheep was compared. Specimens were examined by using a number of potential DC markers (CD11c, CD205, MHC class II (MHCII), CD1b and CD209) in immunohistochemical and multicolour immunofluorescent procedures. The ovine ileal and rectal mucosa contain many CD11c+/CD205+ cells with a dendritic morphology, and the majority of these cells co-expressed MHCII. These double-positive cells were also labelled with the CD209 antibody in the lamina propria and interfollicular regions. Only very few cells expressed CD1b. In conclusion, a major DC population in ileum and rectum of sheep co-expressed the CD11c, CD205 and MHCII molecules. The CD209 antibody appeared to be a novel marker for a subpopulation of ovine intestinal DCs.     

Ontogeny, distribution and structure of aggregated lymphoid follicles in the large intestine of sheep

Aggregates of lymphocytes were demonstrated from 70 days gestation (term 150 days in sheep) in the proximal colon and rectum. Immunoperoxidase staining for 5′-bromo-2′-deoxyuridine incorporation and IgM, indicated that the lymphocyte population of lymphoid follicles in fetal sheep colon was actively dividing and surface IgM positive. Enzyme histochemistry for 5′-nucleotidase showed that the lymphocytes developed in a meshwork of positive reticular cells, suggestive of developing follicles. Follicle aggregates were distributed in a characteristic pattern in lambs, with major accumulations in the ascending colon and in the rectum. In adult sheep a partial atrophy of follicle aggregates was observed. The microscopic structure of large intestinal aggregates showed similarities to the jejunal Peyer's patch (PP), with broad follicles containing a prominent corona and wide interfollicular areas in older lambs. The apparent deep penetration of crypts into the lymphoid tissue proper, which is a frequently reported phenomenon for colon follicles, was dependent on the contractile state of the mucosa, as judged from its absence in specimens where the intestinal wall had been stretched before fixation.     

Response of Leucocyte Populations in the Ileal Peyer's Patch of Fetal Lambs Treated with Ferritin Per Os

A combination of immunohistochemical techniques, a panel of monoclonal antibodies, and computer-assisted morphometric analysis was used to examine the response of the ileal Peyerr''s patch of fetal lambs 7 days after treatment with ferritin per os. Consistent with previous studies in fetal lambs that have reported the ileal Peyer''s patch to be indifferent to antigen, the present study did not find any significant changes in the size of the predominantly B-cell dome/follicle compartment or the predominantly T-cell interfollicular area, nor were differences identified in the distribution of IgM-positive (+), CD4 +, and CD8+ cells in these two compartments. However, both compartments showed a significant increase (P < 0.05) in the percentage of area occupied by MHC II + cells and a significant decrease (P < 0.05) in the percentage of area occupied by CD44+ and B5+ cells. These changes show that the ileal Peyer’s patch of fetal lambs is not indifferent to antigen and may represent the transition of a purely primary lymphoid organ to an organ that has both primary and secondary lymphoid functions.