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Using a new technique for isolating lymphoid cells from the lamina propria of murine small intestine, we have examined the appearance of specific cytotoxic T cells in the gut following intraperitoneal immunization with an allogeneic tumour. Specific cytotoxic T cells appeared in the lamina propria at a time when there are very few cytotoxic lymphocytes in any of the organized lymphoid tissues. Greater levels of cytotoxicity were found in the gut compared with any other site for at least 3 weeks following a single injection of tumour cells. [ABSTRACT FROM AUTHOR]

Spleens from AS × BN donor rats hi belled in vivo by multiple doses of [³H]thymidine were transplanted into syngeneic recipients by anastomosis to the abdominal great vessels. The recipients were killed 1-5 days after receiving the whole spleen transplants and the numbers and location of the [³H]thymidine-labelled cells which had migrated from the labelled donor spleen traced by means of autoradiographs of flections, imprints and smears of various recipient lymphoid tissues. These results were compared with the migration pattern of labelled dissociated spleen cell suspensions injected intravenously. The latter consists almost entirely of small lymphocytes which migrate to T or B areas of recipient spleen, lymph nodes and Peyer's patches. The labeled whole spleens also contained cells which migrated to the T and B areas of recipient lymphoid tissue, but in addition contained many lymphoid cells which migrated to the red pulp of the recipient spleen and to the lamina propria of the gut. These experiments showed, therefore, that the spleen contains mobile elements which have not been detected by transfer of spleen cell suspensions. [ABSTRACT FROM AUTHOR]

We have examined the development of specific cytotoxic T-cell activity in the lungs and the epithelium and lamina propria of the small intestine following tumour cell inoculation by subcutaneous or intraperitoneal routes. After an intraperitoneal injection of tumour cells, large amounts of cytotoxic activity are detectable in the lungs and lamina propria. In comparison, the epithelial lymphocytes of the small intestine display low cytotoxio activity. After a subcutaneous injection, little cytotoxicity is detectable except in the lungs and the development of such cytotoxicity has a much shorter time course compared with that induced by an intraperitoneal inoculation of tumour cells. The data indicate a marked difference in the functional capacity of lymphocytes from the epithelium and lamina propria of the small intestine. [ABSTRACT FROM AUTHOR]

The localization of 125I UdR-labelled mesenteric lymphoblasts and the fraction of the cardiac output delivered to the small intestine was investigated in mice. When different regions of the small intestine were examained, the proportional delivery of the cardiac output and the localization of lymphoblasts were found to vary along the length of the small intestine. A significant correlation between these two phenomena was identified when both lymphoblast localization and the distribution of the cardiac output within the small intestine were studied concurrently. The intestinal localization of populations of unseparated or T-enriched mesenteric lyrnphoblasts and peripheral lymphoblasts all showed a similar degree of correlation with the fraction of the cardiac output delivered along the small intestine in spite of marked differences in their proclivity to accumulate in the gut. We conclude that there is an important relationship in normal animals between the level of lymphoblast accumulation within a particular region of the small intestine and the delivery of blood- borne cells to that region. This relationship could provide a physiological explanation for an anti gent independent yet non-uniform distribution of effector cells within the lamina propria of unimmunized animals. [ABSTRACT FROM AUTHOR]

The migration of [125I]UdR labelled mesenteric (MLN) and peripheral T immunoblasts (PLN) has been followed in mice with multiple sites attractive to immunoblasts. The sites studied were the inflamed gut (produced by Trichinella spiralis infection), inflamed skin, the peritoneal cavity and the mammary glands of lactating mice. PLN were capable of assembling in all of the four sites and in the presence of both inflamed gut and inflamed skin, PLN accumulated preferentially in the skin. MLN, in contrast migrated only to the gut and mammary glands and not to the skin or peritoneal cavity, and could not be diverted from one site to another. Time course experiments revealed that whereas PLN migrate rapidly through the inflamed gut, they are retained in the skin for at least 3 days. [ABSTRACT FROM AUTHOR]

The migration of [125I]UdR-labelled mesenteric lymph node cells in NIH strain mice at various times after infection with the intestinal parasite Trichinella spiralis was investigated. T spiralis produced an enhanced accumulation of mesenteric immunoblasts in the small intestine at 2 and 4 days after infection but not at later times. The enhanced migration occurred when using cells from both uninfected and infected donors, denoting an absence of antigenic specificity. This effect is not secondary to a reduced arrival of cells at sites away from the gut in infected mice, but to a primary increase of the arrival in the small intestine. Mesenteric T lympho- blasts (separated on a nylon-wool column) migrated to the small intestine of uninfected recipients and appear to be a major portion of the population which migrate to the gut of infected recipients. Our results were confirmed using 52 to label mesenteric cells. We conclude that the parasite causes the small intestine to become more attractive or retentive for mesenteric blast cells early during infection. [ABSTRACT FROM AUTHOR]

The factors which determine the migration of lymphoid cells to lamina propria or Peyer's patches of mouse small intestine have been investigated by auto- radiographic tracing of intravenously injected spleen, thymus and lymph node cells. The numbers of labelled cells found in antigen-free grafts of foetal small intestine were compared with the numbers in normally sited gut. Thymus, normal spleen and B spleen lymphocytes, labelled with [³H]adenosine or [5-³H]uridine, were confined to Peyer's patches in normal and grafted gut. [³H]Thymidine-labelled lymphoblasts from the mesenteric nodes of young (19-22 days) mice and mice infected with Nippostrongylus brasiliensis were found in the lamina propria of both graft and normal small intestine, but [³H]thymidine-labelled lymphoblasts from oxazolone-primed lymph nodes did not migrate to the villi. The possible roles of intraluminal antigens, source of cells and changes in cell surface receptors during differentiation, in determining the selective migration of cells to the lamina propria and Peyer's patches, are discussed. [ABSTRACT FROM AUTHOR]

Peripheral blood natural killer (NK) cell activity of a group of 10 healthy non-atopic volunteers was reduced following the topical application of 15 g of 0.1 % betamethasone valerate ointment to the skin nightly for 1 week. In contrast, no such effect was observed when the inactive base of the steroid ointment was used. NK cell activity dropped significantly by day 7 (P<005) and then recovered, although NK cell activity at day 22 was still lower than that observed at the start of the experiment. These findings suggest that topically applied steroid is absorbed in sufficient amounts to cause a systemic effect on NK cell function. This may have implications in a number of dermatological disorders, including atopic dermatitis, where topical steroids form the mainstay of treatment. [ABSTRACT FROM AUTHOR]

The effect of blood transfusion on humoral immunity in chronic renal failure was studied by examining immunoglobulin production in vitro, in patients awaiting renal transplantation. Pokeweed mitogen (PWM) induced IgG plaque formation was normal in non-transfused uraemic patients while both spontaneous and Staphylococcus aureus Cowan I (SAC) induced immunoglobulin production were reduced. Five to ten units of third party blood transfusion reduced PWM-driven B cell differentiation, but had no effect on SAC-induced plaque formation, while spontaneous production of immunoglobulin was either enhanced or unaffected. As it is known that the response to SAC is less affected by suppressor T cell activity than that to PWM, these differences in the inhibitory effects of blood transfusion on B cell differentiation are further evidence that transfusion may act by increasing suppressor T cell activity. [ABSTRACT FROM AUTHOR]

We have investigated the immune responses in vitro of uraemic patients undergoing regular haemodialysis or continuous ambulatory peritoneal dialysis. Twenty-five healthy subjects were also studied as controls. In uraemic patients, the number of T and B lymphocytes were within the normal range, but proliferative respones to phytohaemagglutinin (PHA) were impaired. Spontaneous immunoglobulin plaque forming cell (PFC) responses by peripheral blood mononuclear cells (PBMC) from uraemic patients were significantly lower than those of healthy subjects. The PFC response of uraemic PBMC to the T cell independent polyclonal B cell activator (PBA) Epstein-Barr virus (EBV) was comparable to the response of the healthy subjects, indicating that uraemic B cells are still capable of synthesizing immunoglobulin. Pokeweed mitogen (PWM) induced PFC responses of uraemic PBMC were also normal, whereas the response to another T cell dependent B cell activator, Staphylococcus aureus Cowan I (SAC), was very low. Addition of indomethacin to PWM- and SAC-activated cultures of uraemic PBMC enhanced the PFC response to SAC, but had little effect on the PWM response. As full differentiation of B cells in response to SAC depends on helper T cells, we conclude that a defect in T lymphocyte function accounts for the reduced spontaneous and SAC induced production of immunoglobulin by uraemic PBMC. This defect may be mediated by an indomethacin-sensitive mechanism. [ABSTRACT FROM AUTHOR]

Phagocytosis and degradation of radiolabelled human transferrin-anti-transferrin immune complexes by resident and stimulated mouse peritoneal macrophages was inhibited by liquid infant formula, particularly in the case of resident cells. Mouse peritoneal macrophages exposed to infant formula were shown by immunofluorescence to bind casein and β-lactoglobulin, but there was little binding of α-lactalbumin. Comparison of various artificial milks, cow"s milk and purified casein indicated that both the concentration and the degree of denaturation of casein may be important in the impairment of macrophage function by milk. It is suggested that bottle feeding of infants might result in impairment of macrophage function in the small intestine. [ABSTRACT FROM AUTHOR]

We have investigated whether bacterial lipopolysaccharide (LPS) influences immune responses to dietary protein antigens in experimental animals. Simultaneous intravenous administration of LPS to normal mice fed ovalbumin (OVA) prevented the induction of tolerance for serum IgG antibody responses but did not alter the tolerance of systemic delayed-type hypersensitivity (DTH). In addition, exogenous LPS did not enhance the ability of spleen accessory cells to present OVA to primed T cells. LPS-unresponsive C3H/HeJ mice developed full tolerance of both humoral and cell- mediated immunity after feeding a range of doses of OVA that was equal in degree and persistence to that seen in normal, congenic C3H/HeOla mice and also had normal antigen-presenting cell (APC) activity for OVA. In contrast, C3H/HeJ mice were primed by feeding SRBC instead of developing the systemic tolerance found in normal C3H mice. Our results indicate the complexity of mechanisms that may regulate systemic immunity to orally administered antigens of different forms. Nevertheless, LPS does not modulate DTH responses to fed OVA and does not enhance APC activity, and we conclude that bacterial LPS may be unable to influence hypersensitivity to dietary proteins in man. [ABSTRACT FROM AUTHOR]

Although isolated intraepithelial lymphocytes (IEL) have been shown to have specific and nonspecific cytolytic functions, their ability to proliferate in response to T-cell mitogens or alloantigens is controversial. Here we show that JEL from mouse small intestine do not respond to mitogens such as concanavalin A and phytohaemagglutinin A or in mixed lymphocyte reactions unless an accessory spleen cell is also present. Adherent spleen cells possess the most potent helper function, but a dividing accessory cell may also be required. Supernatants from stimulated lymphocytes also assist IEL to proliferate in vitro, particularly in the presence of adherent accessory cells. IEL could not mediate lethal graft-versus-host disease in irradiated hosts, but could produce popliteal lymph node hypertrophy or splenomegaly in unirradiated hosts. Thus, IEL have the potential for proliferative activities characteristic of T cells, but they require accessory cells and/or factors such as interleukin-2 for their function in vitro and in viva [ABSTRACT FROM AUTHOR]

The localization of 125I-UdR-labelled mesenteric lymph node cells in the small intestine and the fraction of the cardiac output delivered to this organ in mice has been examined. Concurrent measurements of these two phenomena in normal animals showed that there was a significant correlation between the localization of lymphoblasts and the distribution of regional blood flow along the small intestine. In mice undergoing enteric infection with Trichinella spiralis, however, the nature of the connection between lymphoblast localization and blood flow distribution in the small intestine was altered. More lymphoblast label accumulated in the small intestine of infected mice than in uninfected animals even at stages of the infection when no alteration in the proportion of the cardiac output received by the small intestine had occurred. Enhanced lymphoblast accumulation occurred in different segments of the infected small intestine as the infection proceeded and these changes paralleled the way in which the parasite burden was distributed in the intestine. The kinetics of lymphoblast accumulation in infected and uninfected small intestine was examined under circumstances where the delivery of blood-borne Labelled cells was the same. This showed that both increased entry of lymphoblasts and enhanced retention of lymphoblasts occurred in the parasitized small intestine. [ABSTRACT FROM AUTHOR]

The development of cell-mediated immunity to paternally-derived foetal transplantation antigens in parous mice has been assessed by two techniques: skin grafting in an H-2 incompatible mating and a local graft-versus-host assay in an H-2 compatible mating. (1) Lymphoid cells from BALB/c females, parous one to seven times to C3H/Bi males, were injected i.p. into syngeneic males or females which were then grafted with skin from the paternal strain. A slightly accelerated rejection in the adoptively immunized recipients was observed. (2) Lymphoid cells from CBA females, parous one to five times to AKR males, were injected into the feet of young F1 hybrid recipients. The degree of popliteal lymph node enlargement was significantly greater in recipients of cells from parous than from virgin donors. Results using both techniques demonstrated that the development of cell-mediated immunity to paternal transplantation antigens is a regular feature in parous mice and that the degree of immunity increases with successive interstrain pregnancies. [ABSTRACT FROM AUTHOR]

Isografts of foetal small intestine, implanted under the kidney capsules of adult mice grow normally and, despite the lack of intraluminal antigenic stimulation, are populated by thymus-dependent and thymus-independent lymphocytes. The Peyer's patches in these grafts are very small, lack germinal centres and can be shown to have small thymus-dependent areas. Quantitative intraepithelial lymphocyte counts were carried out in normally sited small intestine of immunologically intact and thymus-deprived mice, and in grafts implanted in intact and thymus-deprived mice. Counts were also performed in a group of neonatally thymectomized and control mice. The results show a significant depletion of intraepithelial lymphocytes in neonatally thymectomized mice, and a profound reduction in numbers of intraepithelial lymphocytes in grafts, deprived of antigen, when compared with normally sited intestine of the same age. [ABSTRACT FROM AUTHOR]

The effect of cortisone acetate on specific cell mediated immunity in mice was investigated using contact sensitivity to oxazolone. A long-acting cortisone acetate preparation was found to be much more effective than a soluble preparation in suppressing temporarily the recall response to oxazolone. The long-acting preparation was also effective in inhibiting the induction of sensitivity when injected before (but not after) oxazolone. Removal of the thymus either before or after sensitization did not significantly enhance the effects of cortisone acetate, and it is therefore suggested that cortisone acetate acts independently of the thymus-derived lymphocyte population. [ABSTRACT FROM AUTHOR]

It is now accepted that there are present within the peripheral lymphoid tissues of the mammal, lymphocytes which differ in their origin, migratory patterns and lifespan; two major groups have so far been defined, one of thymus-dependent or thymus-derived lymphocytes and another of thymus-independent or bone-marrow derived lymphocytes. These cells which are morphologically indistinguishable when free float lug in the blood or lymph nevertheless segregate from one another into clearly defined compartments whilst resident in or passing through the lymph nodes, spleen or Peyer's patches. The purpose of this article is to summarize some of the experimental evidence for this segregation and to discuss its physiological and immunological implications, it is not intended to be an extensive review of the literature. [ABSTRACT FROM AUTHOR]

Normal, 'deprived' (thymectomized, irradiated, bone marrow injected) and 'reconstituted' (thymectomized, irradiated, bone marrow injected, thymus grafted) CBA mice have been tested for their ability to respond to the contact sensitizing agent, oxazolone. The test involved painting the ear of a previously sensitized animal and subsequently measuring alterations in ear thickness. .A sensitized condition could be detected in the normal and reconstituted mice after either one or two sensitizing contacts with oxazolone but in the deprived animal little or no sensitivity could be detected. It is concluded, that the thymus influences the development of contact sensitivity probably by provision of a population of reactive cells. [ABSTRACT FROM AUTHOR]

Thymus was labelled in vivo by injecting newborn C3H/Bi mice with three or four doses of 2 μc of [3H]thymidine. The labelled thymus was grafted into the kidney capsule of 22-25-day-old intact and thymectomized syngeneic recipients which were killed 18, 41 or 42 days later. The grafts and lymphoid tissue were sectioned and examined by autoradiography after exposure times of up to 26 weeks. Small and medium labelled lymphocytes were seen in the thymus-dependent areas of the lymph nodes and spleen of all recipients provided the sections were exposed for a sufficiently long period. More labelled cells were seen in recipients killed at 18 days than at 41 or 42 days after grafting. It was concluded that these cells were the direct descendants of those cells labelled in the graft. There was no evidence of re-utilization of the isotope label. Most of the cells originally labelled in the graft either lost their label by multiple divisions or were replaced by unlabelled cells; although the epithelial-reticular cells remained heavily labelled. The importance of this last finding is discussed. [ABSTRACT FROM AUTHOR]

A method of orthotopic ovarian grafting in a stock of hooded rats has been described. Intra-strain grafts were established in ten out of eighteen animals and six of these were fertile. Four fertile rats were killed during their first pregnancy but two others kept for 120 and 154 days had several litters of normal size. When ovarian tissue from donors from a stock of albino rats was implanted orthotopically into hooded recipients all the grafts were overwhelmed by homo-graft reaction within 24 days. However, both inter- and intra-strain grafts persisted in the subcutaneous site. Factors affecting the establishment and fertility of the intra-strain orthotopic grafts have been discussed and an explanation for the difference in host response to incompatible grafts according to the site of implantation has been suggested. [ABSTRACT FROM AUTHOR]

The article presents information on the lymphoid tissues in Mice with congenital aplasia of the Thymus. The lymph nodes, spleens and Peyer's patches from seven nititant tm nu mice with agenesis of the thymus were compared with similar tissues from eight phenotypically normal littermate controls. In all lymph nodes examined from the nu nu mice the thymus-dependent areas were virtually "empty" of lymphocytes. In the corresponding areas in the spleen and Peyer's patches the numbers of lymphocytes were also significantly reduced. The thymus-dependent areas in all the lymphoid tissues examined in the homozygous nu nu mice with congenital aplasia of the thymus contained very few if any lymphocytes. These observations, therefore, substantiate the previous conclusions that there is a specific population of lymphocytes whose normal development depends upon the presence of the thymus.

The article presents a study, where comparing the effects of neonatal thymectomy on New Zealand Black (NZB) mice, he possible role of thymus in autoimmune disease was discovered. The neonutally thymectomized NZB mice, in common with those of other strains, showed lethal wasting, a lymphocyte deficit in their lymphoid organs and blood, their packed cell volume was reduced and some had liver lesions associated with the hepatotrophic virus MHV-l. Although germinal centers develop and plasma cells occur in the lymphoid organs of most thymectomized mice, the striking feature of the NZB mice was the large number, size and activity of the germinal centers that persisted after thymectomy.