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D M Parrott

Publications and source records attributed to D M Parrott.

At least 55 records · Page 3Linked to original sources

Preparation and purification of lymphocytes from the epithelium and lamina propria of murine small intestine.

Existing methods for the production of lymphocytes from the small intestine have proved unsatisfactory when applied to the mouse. We report here a new method for the production of highly pure suspensions of lymphoid cells from the epithelial layer and lamina propria of mouse small intestine. The production and purification methods are described in detail. At least ten million lymphocytes are obtainable from each small intestine from either the epithelium or lamina propria and the cell suspensions are shown to be little contaminated by non-lymphoid cells. Preliminary analysis of the two cell types indicates that they belong either to two separate populations or to one population in very different stages of differentiation. The use of purified lymphoid cells from the epithelium and lamina propria of the small intestine may enable examination of the generation of cytotoxicity towards gut epithelial cells; this may be important in the development of inflammatory bowel diseases.

Age Factors↗

Cytotoxic T cells in small intestine epithelial, lamina propria and lung lymphocytes.

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 cytotoxic 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.

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The early appearance of specific cytotoxic T cells in murine gut mucosa.

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 allogenic 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.

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Regional blood flow and the localization of lymphoblasts in the small intestine of the mouse. I. Examination of normal small intestine.

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 examined, 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 lymphoblasts 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 a antigen-independent yet non-uniform distribution of effector cells within the lamina propria of unimmunized animals.

Animals↗

Regional blood flow and the localization of lymphoblasts in the small intestine of the mouse. II. The effects of a primary enteric infection with Trichinella spiralis.

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.

Animals↗

Regional blood flow and its relationship to lymphocyte and lymphoblast traffic during a primary immune reaction.

The relationship of alterations in blood flow with changes in cell distribution has been studied in an inflammatory site and its draining lymph node during the induction of an immune reaction with oxazolone in mice. The cells which move to the site of inflammation are predominantly lymphoblasts and their increased localization in the inflamed ear is significantly correlated with increased regional blood flow to the inflamed tissue. The existence of this correlation is not antigen dependent although there is a relative increment of lymphoblasts which are specifically primed to the inflammatory agent. The localization of nonblastic (small) 51Cr-labeled lymphocytes on the other hand is substantial only in lymphoid tissue and during the induction of an immune reaction after oxazolone application, the increase in localization of these cells in the draining lymph node is positively correlated with increased blood flow to the node. Furthermore, the probability of finding 51Cr labeled lymphocytes in a particular lymph node is related to the regional blood flow which that node receives.

Animals↗

Migration of lymphoblasts to the small intestine. III. Strain differences and relationship to distribution and duration of Trichinella spiralis infection.

In NIH strain mice, in which the majority of Trichinella spiralis are located in the anterior half of the small intestine early in the enteral phase of infection, enhanced localization of mesenteric lymphoblasts, nylon wool separated mesenteric T-lymphoblasts and even oxazolone sensitized peripheral lymphoblasts is most prominent in the anterior region of the small intestine. As the worms move to the posterior half of the small intestine, enahnced localization of lymphoblasts is observed in that region only. In BALB/c mice, in which most of the worms are located in the posterior half of the small intestine, enhanced localization of lymphoblasts is primarily in that region. Expulsion of the worms commences within 2--3 days of a large increase in the number of lymphoblasts localizing in the anterior region of the small intestine in NIH strain mice and likewise follows a second and larger increase in the number of lymphoblasts localizing in the posterior region of the small intestine of BALB/c mice.

Animals↗

Heterogeneity of locomotion in human T cell subsets.

Locomotor activity of T cells with receptors for IgM and IgG, T cells without receptors for IgM or IgG, and T and non-T cells from human peripheral blood and human tonsils towards the chemoattractant casein was examined in modified Boyden chambers. T cells with receptors for IgG both from human tonsils and peripheral blood did not move in response to casein. T cells with receptors for IgM and those without receptors for IgM or IgG, on the other hand, moved very well toward casein and the distances were comparable to those achieved by T cells before separation. This difference in the locomotor activity of T cell subsets might explain their differential distribution in various lymphoid compartments. Separated T cells, cultured in medium supplemented with fetal calf serum, moved into the filters in response to casein. Prior culture of T cells in medium alone or in medium supplemented with human AB serum resulted in a reduction in the distance traveled in response to casein; however, the effect of AB serum was variable. Non-T cells from peripheral blood and B cells from tonsils responded poorly to casein.

B-Lymphocytes↗

The accumulation of immunoblasts in extravascular tissues including mammary gland, peritoneal cavity, gut and skin.

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.

Animals↗

Antigen-induced locomotor responses in lymphocytes.

The effect of protein antigens on the locomotion of lymphocytes from the lymph nodes draining the site of antigenic challenge in immunized mice, and from the same nodes in control mice, was studied in filters using a checkerboard assay in which the absolute concentration and the concentration gradient of attractant was varied in a series of chambers. Serum albumin (HSA or BSA) was chemokinetic for unimmunized lymphocytes inasmuch as the distance migrated into filters by cells in its presence varied with the absolute concentration of albumin, but not with the concentration gradient, indicating an influence of the serum albumin on the rate but not on the direction of locomotion. Ovalbumin and nonalbumin proteins did not show this effect. Using the same assay, the migration of primed lymphocytes in the presence of the priming antigen was shown to be influenced by the antigen gradient in a way that suggested a positive chemotactic response of the lymphocytes to antigen. This response was only shown clearly when the cells were in a chemokinetic medium containing serum albumin.

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