1. The development and functions of the gut-associated lymphoid tissues has been studied in foetal sheep and lambs.
2. The Peyer’s patches were first detected histologically in the jejunum of foetal lambs at 70 day’s gestation and in the ileum at about 120 days gestation. At birth the Peyer’s patches were mature morphologically and their lymphoid follicles contained many pyroninophilic cells in mitosis. Most cells in the Peyer’s patch follicles became labelled following a single injection of 3 H-thymidine intravenously.
3. The mesenteric lymph nodes can be identified macroscopically at 60 days gestation and they develop in size throughout gestation. The cortex and medulla of the mesenteric nodes do not become clearly differentiated until after birth. After birth the growth of the mesenteric nodes is significantly faster than the growth of other lymph nodes.
4. There are few lymphocytes in the lamina propria and in the epithelium of the intestines before birth and no plasma cells. After birth the number of lymphocytes in both theses sites increases and many blast cells and plasma cells appear in the lamina propria.
5. The epithelium overlying the domes of the Peyer’s patches was found to take up particulate material from the lumen of the gut. Colloidal carbon passed into the epithelial cells overlying the domes, thence into phagocytic cells within the domes. Colloidal carbon did not enter the epithelial cells overlying the villi.
6. The development of the Peyer’s patches proceeded in utero in the absence of antigenic stimulation and in the absence of immunoglobulins. Injection of B. abortus organisms, ferritin or material colostrum into the gut of foetal lambs had no apparent effect on the development of the Peyer’s patches. The structure of the mesenteric nodes was modified by the injection of antigen into the gut and caused plasma cells to appear in these nodes and in the lamina propria of the gut.
7. During the first 1-2 months of postnatal life the Peyer’s patches increased rapidly in size and there was an increase in the density of pyroninophilic cells in their follicles. These changes did not occur in the Peyer’s patches of sterile antigen-free segments of ileum isolated from the intestinal tract one month before birth. In these isolated intestinal segments the Peyer’s underwent premature regression after birth so that by 3-4 months they had disappeared apart from the dome regions and the interfollicular areas.
8. When isolated ileal segments with regressing Peyer’s patches were rejoined to the functional gut, the Peyer’s patches were rejuvenated and restored to their normal morphological appearance provided they had not regressed beyond a certain critical point.
9. In utero thymectomy done on the foetuses of 60 days gestation reduced the development of Peyer’s patches in some but not all lambs. In thymectomised lambs the inerfollicular areas were depleted of cells and the follicles were smaller at birth and regressed more rapidly than in normal lambs.
10. The cells in the thoracic duct lymph of foetal lambs in utero was found to be almost exclusively small lymphocyte, very few of which incorporated 3 H-thymidine. Within a short time after birth, this cell population cane to contain many blast cells and cells in mitosis which were derived from the gut-associated lymphoid tissues.
11. The source of these blast cells was examined in mesenteric lymphadenectomized lambs. The Lymphoid cells in lymph collected directly from the intestines were similar to the cells on lymph efferent to the mesenteric nodes. Removal of the mesenteric nodes had little effect on the output of cells in the intestinal lymph. This result suggested that the Peyer’s patches were a major source of the free-floating cells on blood and thoracic duct lymph in the lambs.
12. The output of cells in the intestinal lymph of lambs thymectomized in utero was lower than in normal lambs.
13. Studies on the recirculation pattern of cells collected from the intestinal lymph demonstrated that both small and large lymphoid cells derived from the gut recirculate rapidly between the blood and lymph. This held for cells collected from intestinal lymph in both normal and mesenteric lymphadenectomized lambs. Large lymphoid cells and blast cells recirculated more rapidly than did small lymphocytes.
14. When small lymphocytes collected form the intestinal lymph were injected intravenously they were detected subsequently in large numbers in various lymph nodes throughout the body and in the spleen, in the dome regions and in the interfollicular areas of the Peyer’s patches.
15. Large lymphoid cells and blast cells collected from the intestinal lymph showed a predilection to localize in the mesenteric lymph nodes and in the gut, in particular in the lamina propria. In these situations many of these cells differentiated into plasma cells. Many more large lymphoid cells and blast cells localized in the normal functional gut than in sterile antigen-free segments of intestine that had been isolated from the functional gut since before birth.
16. Cells generated in the Peyer’s patches were found to return to the gut in large numbers after they were injected intravenously, establishing a specific homing pattern for these cells which determined that their origin and life history was linked to the gut. This process determined that cells originated in specific localized areas of lymphoiesis in the gut subsequently became re-distributed along its entire length.