The intestinal intra-epithelial lymphocytes (IEL) are divided into several subsets on the basis of expression of T cell receptor (TCR) alpha beta and gamma delta, intensity of Thy-1 expression and expression of Lyt-3 chain. To investigate the differentiation pathway of the IEL, we examined the repertoire of V beta segments of T cells in the IEL in BALB/c (H-2d, MIs-1b2a) or AKR/J (H-2k, MIs-1a2b) mice. Among freshly isolated IEL, an appreciable number of T cells bearing V beta 3 or V beta 11, which recognize MIs-2a- or MHC IE-encoded molecules respectively, were detected in BALB/c mice. Similarly, in AKR/J mice, IEL contained appreciable levels of V beta 6-bearing T cells. V beta 3- or V beta 11-bearing T cells in the IEL in BALB/c mice increased to a significant level when incubated with staphylococcal enterotoxin A which specifically stimulates V beta 3- and V beta 11-bearing T cells. Most of IEL without clonal deletion expressed Lyt-2 but not Lyt-3 antigens. Such T cells were hardly detected in other organs, including liver. Our results indicate that TCR alpha beta-bearing intestinal IEL that have not undergone negative selection may have differentiated outside the thymus, presumably at a local site of the intestine and can respond normally to the signal via their TCR.

By introducing an interaction energy function, the first two of the present authors proposed a one-dimensional pseudoelastic theory of shape memory alloys, which has been demonstrated to model complicated experimental results and Tanaka's transformation kinetics qualitatively well.To study the stress-strain-temperature relationship, we will further develop the pseudoelastic theory by introducing temperature-dependent terms in the free energy function proposed by Ranieki and Bruhns. In addition, the effect of temperature is included in the interaction energy. For computational analysis, material parameters are estimated from data measured by Tobushi and his coworkers in their experiments. Numerical results show that predictions by the present theory agree with some essential feature of their experimental results.

Oral administration of "immune milk", that had been obtained from cows immunized with a variety of human gut bacteria containing E. coli, S. typhimurium, S. dysenteriae and 23 others, protected AKR/J mice from the lethal effect of radiation, when immune milk was orally given to mice at 150 g kg-1 day-1 for 7 days prior to gamma-irradiation of 8 Gy. Mean survival times were 24.8 days for the group given immune milk but only 16.8 days for the group given control milk from unimmunized cows. Enterobacteriaceae were detected in various organs such as liver, lung and kidney on day 13 after irradiation, whereas the numbers were significantly fewer in the study group as compared with the control group. And fewer number of intestinal Enterobacteriaceae were detected in the study group compared with the control group prior to irradiation. Immune milk also enhanced the mitogenic response to mesenteric lymph node cells, the redirected cytolytic activity of intestinal intraepithelial lymphocytes to P815 tumor cells with anti-CD3 mAb, and in vitro killing activities of the phagocytes in mesenteric lymph nodes to E. coli as compared with control milk. These results suggest that immune milk may reduce the number of bacteria translocating from the intestinal-tract and augment the activities of the gut-associated lymphoid tissues against the invasion of intestinal bacteria, causing protection against the lethal effect of radiation.

Autoimmune disease-prone (NZB x NZW)F1 (B/W) female mice are a model of human lupus erythematosus. Immune milk, obtained from cows immunized with various intestinal bacterial antigens, was given to B/W mice as a component of diets beginning at 8 wk of age. Diets were fed ad libitum or restricted to 60% of ad libitum energy intake. Controls were fed commercial skim milk. In B/W mice fed ad libitum, the titers of anti-single-stranded DNA antibodies were significantly lower in immune milk-fed mice at 4 and 6 mo of age. Onset of proteinuria was delayed and life span was significantly prolonged by immune milk feeding. Surface phenotypes of the T cells and levels of the responsiveness of lymphocytes to mitogens were not changed by immune milk feeding. The B/W mice restricted to 60% of ad libitum energy intake, which preserved immune responsiveness, had not developed proteinuria by 14 mo of age, irrespective of immune milk feeding or control milk feeding. However, at 10 mo of age, the level of plasma antibodies against intestinal bacteria was significantly higher in energy-restricted mice fed control milk than in those fed immune milk or in mice fed ad libitum.

Milk was obtained from nonimmunized cows and cows immunized with a mixture of various human gut bacteria. Each milk was administered orally to 2-mo-old C57BL/6 mice at a dose of 150 g.kg-1.d-1 for either 6 or 16 mo. The study group had fewer enteric bacteria and a lower concentration of the serum antibodies against enteric bacteria compared with the control group at 8 and 18 mo of age. Furthermore, the study group at 18 mo old had a higher redirected cytotoxicity of intestinal intraepithelial lymphocytes, a higher proliferative response of mesenteric lymph nodes cells against mitogenic or alloantigenic stimulation and a greater ability of the spleen cells to produce anti-sheep erythrocytes IgG antibody after systemic immunization with sheep erythrocytes. A lower level of autoantibodies was observed at 8 mo and 18 mo of age in the study group compared with the control group. These results suggest that the senescence of the murine immune system may be delayed by consumption of milk from immunized cows.