Biomedical subjects

E A Washington

Publications and source records attributed to E A Washington.

At least 19 recordsLinked to original sources

PubMed2001

Instillation of 3% hydrogen peroxide or distilled vinegar in urethral catheter drainage bag to decrease catheter-associated bacteriuria.

Patients with indwelling catheters acquire urinary tractinfections ata rate of 5% perday. After 30 days of catheterization, there is a 78% to 95% incidence of bacteriuria, despite the use of meticulous catheter care. Research studies on reducing the development of bacteriuria have focused on the propagation of bacteria within the catheter drainage bag. This research proposal sought to determine the effects of instillation of 3% hydrogen peroxide versus distilled vinegar in urethral catheter drainage bags to decrease bacteriuria in 20 long-term catheterized patients. Baseline urine cultures for control and test mediums showed no significant difference in rates of bacteriuria. However, urine cultures obtained at the 48-hour interval showed significant reduction in bacteriuria in urinary bags irrigated with vinegar The implications this study has for nursing practice include a needforfurther research using a larger number of subjects and a need for improvements in the design of the catheter drainage system.

Acetic Acid↗

PubMed1999

Regulation of T cell homeostasis during fetal and early postnatal life.

Before parturition the fetal lamb develops a large pool of long-lived recirculating T cells which provides a large population of naive T cells with a diverse TcR repertoire. After birth and concomitant with exposure to environment antigens, fetal T cells are rapidly replaced by short-lived cells formed postnatally. The majority of thymic emigrants homing to spleen in postnatal lambs are short-lived, in contrast to emigrants targeting lymph nodes where a population appears to be long-lived. The lifespan of thymic emigrants in the fetus is unknown as in the relative importance of antigen-driven processes versus developmental programming in regulating T cell homeostasis in early postnatal life.

Age Factors↗

PubMed1999

The ontogeny of T cell recirculation during foetal life.

Studies on the ontogeny of the immune system in the sheep foetus, which remains immunologically naive until after birth, indicate that a large scale recirculation of T cells is just as much a feature of the foetal immune system as it is in animals after birth. An extensive recirculation of T cells and dendritic cells through peripheral tissues-including the gastrointestinal tract and skin-develops early in foetal life, although a population of gut-homing memory T cells does not develop until postnatal life. Current evidence suggests that two populations of thymic emigrants with distinct tissue-homing specificities to spleen and lymph node contribute to the development of the foetal peripheral T cell pool. CD8(+) thymic emigrants mostly target spleen while CD4(+) thymic emigrants home predominantly to lymph nodes. The lifespan of thymic emigrants is uncertain, although cells entering lymph are long-lived and form the basis of a diverse pre-immune repertoire of recirculating T cells. The life history and growth rates of non-recirculating T cells in spleen and lymph nodes during foetal life are at present unknown.

Animals↗

PubMed1999

L-selectin expression on thymic emigrants defines two distinct tissue-migration pathways.

We have studied the appearance and phenotype of recent thymic emigrants in blood, spleen and lymph nodes (LN) of neonatal lambs. Using in situ labelling of thymocytes with fluoroscein isothiocyanate (FITC), we examined the expression of the LN homing receptor L-selectin on alphabeta and gammadelta subsets of recent thymic emigrants 24 hr after labelling. There were marked differences in the proportions of CD4+, CD8+ and gammadelta T-cell receptor (TCR+) cells exported from the thymus to spleen compared to lymph nodes. Spleen was enriched in CD8+ and gammadelta TCR+ emigrants while LN were enriched in CD4+ emigrants. There were also marked differences in the expression of L-selectin by emigrants homing to spleen compared with those homing to lymph nodes. While the majority of thymic emigrants in LN expressed L-selectin, considerably fewer emigrants in spleen were L-selectin+. The presence of large numbers of CD8+ L-selectin- and gammadelta TCR+ L-selectin- thymic emigrants homing to spleen raises the possibility that unique homing receptor specificities underpin the migration of T cells to spleen as distinct from lymph nodes.

Animals↗

PubMed1997

An immune system switch at birth triggers a change in the lifespan of peripheral T cells.

Lymphocyte recirculation is an essential element in the integration of immune responses and is an absolute requirement for the development of systemic memory in postnatal animals. During foetal life a large pool of recirculating T cells develops and migration pathways of naive T cells to skin and peripheral tissues as well as LN are established. At birth a process is triggered whereby naive fetal T cells are rapidly lost from the circulating pool and are replaced by newly arriving T cells which have been formed since birth. At present our data suggest that the thymic export in the fetus creates a pool of long-lived naive T cells of wide diversity. The situation in neonatal lambs is more complex since the thymus is exporting large numbers of short-lived thymic emigrants which enter a peripheral T-cell population where many T cells are dividing.

Animals↗

PubMed1997

An immune system switch in T cell lifespan at birth results in extensive loss of naive fetal T cells during the first week of postnatal life.

Lymphocyte recirculation is critical to maximize the efficiency of immunological surveillance and is an absolute requirement for the development of systemic memory. The consensus view of the lifespan of peripheral T cells holds that naive T cells are long-lived cells and most memory T cells are short-lived cells, although the question of the lifespan of peripheral T cells is not yet fully resolved. We have studied the lifespan of T cells circulating in efferent lymph draining lymph nodes (LN) in the immunologically naive sheep fetus and in postnatal lambs immediately following birth by examining the in vivo incorporation of [3H]thymidine by newly formed T cells during continuous administration of [3H]thymidine. We report that authentically naive fetal T cells are long-lived cells which continue to recirculate between blood and lymph during fetal life. At birth, however, a process is triggered whereby fetal T cells circulating through LN are rapidly lost from the peripheral T cell pool and are replaced by freshly arriving T cells which have been formed since birth. Our results indicate that by the end of the first week of postnatal life, around three-quarters of the T cells circulating through peripheral LN have been formed since birth.

Animals↗

PubMed1996

Origin and development of the gamma delta T-cell system in sheep: a critical role for the thymus in the generation of TcR diversity and tissue tropism.

Ruminant gamma delta T cells are concentrated at epithelial surfaces and share many features in common with species such as mice and humans which contain relatively fewer gamma delta T cells than ruminants. To date no gamma delta T cells with invariant TcR have been found in sheep and the generation of gamma delta TcR diversity which is thymic dependent follows a developmentally regulated sequence. Analysis of thymic export of gamma delta T cells shows that emigration of gamma delta T-cell subsets increases markedly during fetal life and after birth suggesting intrathymic processes leading to mature gamma delta T cells may change during development. Skin homing gamma delta T cells acquire their tissue tropism inside the thymus and pathways of recirculation of gamma delta T cells to skin are laid down during fetal development independent of antigen and remain stable through into adult life.

Animals↗

PubMed1996

Late-term fetal thymectomy does not prevent the development of gut-homing T cells after birth.

Tissue-specific circulation of T cells is a critical element in the integration of systemic immune responses. Current models of T-cell migration suggest that homing specificities of T cells for tissues such as gut and skin are generated outside the thymus as a result of activation of virgin T cells by antigen in lymph nodes. We have used the sheep fetus (which is immunologically virgin and contains no memory or effector T-cell subsets) to examine the migration of 51Cr-labelled T cells in vivo. We report that gut-homing T cells are not present in the fetus and that gut-homing T cells from postnatal lambs home normally to fetal gut. Fetal thymectomy performed immediately prior to birth failed to prevent the development of gut-homing T cells in postnatal life. Gut-homing specificities on T cells are thus acquired extrathymically.

Animals↗

PubMed1995

Role of the thymus in the generation of skin-homing alpha beta and gamma delta virgin T cells.

Current models of lymphocyte traffic suggest that homing specificities of T cells to tissues such as skin are generated outside the thymus as a result of activation of naive T cells by antigen in lymph nodes. Virgin T cells are thought to home to high endothelial venules in lymph nodes, but are thought to be unable to home to extra-lymphoid tissues such as skin. We used the technique of in situ labeling of the thymus with fluorescein isothiocyanate to examine the homing specificities of authentically naive T cells in vivo, immediately after their export from the thymus. We report that homing specificities for skin as well as lymph node are imprinted on T cells inside the thymus, independent of antigen. We also show that both alpha beta and gamma delta emigrant T cells exhibit homing patterns to skin and lymph nodes which are identical to those of mature T cells. Our findings demonstrate a key role for the thymus in the induction of skin-homing specificities on T cells indicating that skin-homing specificities of T cells are not generated solely outside the thymus as a result of the activation of virgin T cells by antigen. The migration of thymic emigrants to extra-lymphoid tissues within a few hours of leaving the thymus may have implications for mechanisms of peripheral self-tolerance. This pathway provides an opportunity for direct virgin T cell interactions with self components only expressed in the periphery at a time when emigrants may be more susceptible to tolerance induction than mature circulating T cells.

Animals↗

PubMed1995

Virgin alpha beta and gamma delta T cells recirculate extensively through peripheral tissues and skin during normal development of the fetal immune system.

Current models of T cell migration place severe restrictions on the recirculation of virgin T cells, condemning them to migrate exclusively via high endothelial venules in lymph nodes until they either die or acquire the capacity to migrate to skin and peripheral tissues as memory cells following stimulation with antigen. We have demonstrated in the sheep fetus (which is immunologically virgin until after birth) that virgin T cells and dendritic cells circulate through skin and peripheral tissues during fetal life in the same non-random manner as adult T cells but in much larger numbers than they do in adult animals. Our data also showed that T cells do not discriminate between peripheral tissues and skin or lymph nodes on the basis of virgin or memory CD45R phenotype, or CD2, CD58 or CD44 phenotype, and with the possible exception of CD11a/CD18, that it is not mandatory for lymphocytes to be activated to adhesion moleculehi status in order to home to fetal skin. Our results indicate that unique tissue-homing specificities for extra-lymphoid tissues can be imprinted on virgin T cells independent of foreign antigen. Virgin T cells have previously been thought to be denied access to peripheral tissues; however, the large-scale traffic of virgin T cells through extra-lymphoid tissues in the fetus reported here provides a mechanism whereby direct virgin T cell interactions with self-antigens expressed only on tissues outside the thymus can occur repeatedly during development of the fetal immune system.

Age Factors↗

PubMed1994

Differences in the tissue-specific homing of alpha beta and gamma delta T cells to gut and peripheral lymph nodes.

Tissue-selective streaming of T cells is considered to be a critical element in the integration of normal immune responses in intact animals. The results presented in this paper show that while there were major subsets of gut-homing T cells present in intestinal lymph, there were considerable differences in the tissue tropism of T cell populations circulating in lymph draining gut and peripheral lymph nodes. Thus, while CD4+ cells returned preferentially to their tissue of origin, gamma delta T cells showed a strong migratory preference for peripheral lymph nodes regardless of their tissue of origin. In contrast, although a population of gut-homing CD8+ cells was present in ileal lymph, CD8+ T cells from peripheral lymph nodes homed equally well to gut and lymph nodes. There were also considerable differences in the expression of L-selectin on T cells circulating in the two compartments. L-selectin was down-regulated on alpha beta T cells present in ileal lymph but not on gamma delta T cells which expressed the highest levels of L-selectin of all T cell subsets. It is suggested that gut-homing alpha beta T cells which have down-regulated L-selectin are formed in the gut-associated lymphoid tissues in response to gut antigens while the migratory properties of gamma delta T cells are ontogenetically determined, independent of antigen.

Animals↗

PubMed1990

Nonrandom migration of CD4+, CD8+, and gamma delta+T19+ lymphocyte subsets following in vivo stimulation with antigen.

We report here the results of experiments in which the migration of three T cell subsets (CD4+, CD8+, and gamma delta+T19+ cells) through antigen-stimulated lymph nodes and subcutaneous granulomas has been compared with that through normal skin and resting lymph nodes. The percentage of gamma delta+T19+ lymphocytes was halved and the percentage of CD8+ lymphocytes was doubled in lymph draining stimulated compared with control tissues, and all lymphocyte subsets except gamma delta+T19+ lymphocytes had higher hourly outputs in lymph draining antigen-stimulated compared with control tissues. Antigen also resulted in a higher percentage of CD8+ lymphoblasts and a lower percentage of gamma delta+T19+ lymphoblasts in efferent lymph draining antigen-stimulated lymph nodes. The data indicate that lymphocyte subsets leave the blood with differing efficiencies in different vascular beds and raise the possibility that antigen can influence the rate at which tissues extract individual T cell subsets from the blood.

Animals↗

PubMed1990

Non-random migration of CD4+, CD8+, gamma delta + T19+, and B cells between blood and lymph draining ileal and prescapular lymph nodes in the sheep fetus.

We have examined the circulation of CD5+, CD4+, CD8+, gamma delta + T19+, and B cells through ileal and prescapular lymph nodes in the sheep fetus in an environment uninfluenced by foreign antigen and ongoing immune responses or circulating immunoglobulins, and have contrasted this circulation with that occurring through the same tissue in 1-year-old sheep. The vast majority of lymphocytes circulating through fetal prescapular lymph nodes and fetal ileal lymph were T cells; however, there was a significantly higher concentration of B cells in ileal lymph compared to prescapular lymph. Furthermore, in contrast to 1-year-old sheep, there was an imbalance in the distribution of CD4+ cells and CD8+ cells in fetal prescapular and ileal lymph, with CD4+ cells enriched in prescapular lymph relative to other T cell subsets and CD8+ cells enriched in ileal lymph. Our results suggest that in the fetus either there is preferential migration of CD4+ cells through peripheral lymph nodes and/or CD8+ lymphocytes through the ileal gut, or newly formed CD8+ lymphocytes are being released from the ileum or ileal lymph node directly into ileal lymph.

Animals↗

PubMed1990

Non-random recirculation of small, CD4+ and CD8+ T lymphocytes in sheep: evidence for lymphocyte subset-specific lymphocyte- endothelial cell recognition.

The migratory properties of small, CD4+ and CD8+ T lymphocyte subsets have been examined in sheep under physiological conditions. Lymphocytes obtained free-floating in lymph were directly labeled with fluorochrome in vitro and returned to the blood of the same animal. Over the next 48 h the lymph collection bottles were replaced at various times. The cells in these collections, as well as an aliquot of the cells used for direct fluorescent labeling, were then phenotyped with monoclonal antibodies (mAbs) which define the mutually exclusive CD4+ and CD8+ T lymphocyte subsets in sheep. Binding of mAbs was detected by using secondary reagents labeled with a fluorochrome of a different colour. All cell samples were analyzed by flow cytometry and CD4/CD8 ratios were determined for the recirculated, fluorochrome-labeled population in each lymph collection. The mean CD4/CD8 ratio was then calculated and compared with the CD4/CD8 ratio of the intravenously infused starting population. In three experiments employing efferent prescapular lymph cells, three experiments employing efferent intestinal lymph cells and two experiments employing afferent intestinal lymph cells, the mean CD4/CD8 ratio of the recirculated, fluorochrome-labeled population was different from the CD4/CD8 ratio of the starting population, thereby indicating that non-random migration of these subsets had occurred. The finding that the CD4/CD8 ratio of the recirculated population was higher than the CD4/CD8 ratio of the transfused starting population in every case provides strong experimental support for the hypothesis that small, CD4+ T cells are extracted from the blood by specialized vascular endothelium with greater efficiency than small, CD8+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Non-random migration of CD4+, CD8+ and gamma delta+T19+ lymphocytes through peripheral lymph nodes.

The experiments described in this paper have examined the migration of three fluorochrome-labelled T-lymphocyte subsets (CD4+, CD8+ and gamma delta+T19+) on a single passage from blood to lymph, through prescapular lymph nodes. Lymphocytes obtained from prescapular efferent lymph were labelled in vitro with fluorochrome and returned to the blood of the same animal. Over the next 2 days, lymph was continuously monitored and the cells in all collections, including the one used for intravenous infusion, were phenotyped and analysed by flow cytometry. Significant differences in the subset ratios between the infused, starting population and the recirculated population indicated that CD4+ and gamma delta+T19+ lymphocytes are extracted by a resting lymph node at the same rate and that both are extracted at a faster rate than CD8+ lymphocytes. The results presented here also suggest that a unique subset of gamma delta+T19+ lymphocytes may be present in blood that does not recirculate through peripheral lymph nodes.

Animals↗

PubMed1989

Recirculation of lymphocyte subsets (CD5+, CD4+, CD8+, SBU-T19+ and B cells) through gut and peripheral lymph nodes.

The surface phenotypes (CD5+, CD4+, CD8+, SBU-T19+, MHC class II+, T80+ and sIg+) of lymphocytes in blood, and in prescapular and ileocaecal efferent lymph of sheep, have been determined. The similarity in the distribution of lymphocyte subsets in both lymph compartments indicated that the non-random migration of lymphocyte populations to peripheral lymph nodes and gut could not be due to preferential migration of a particular lymphocyte subset such as CD4+ or CD8+ cells to one tissue. Marked differences in the percentage of lymphocyte subsets between blood and efferent lymph suggested that some lymphocyte subsets leave the blood with differing efficiencies and that differential extraction of lymphocyte subsets from blood by a lymph node may be due to subset-specific lymphocyte-endothelial interactions.

Animals↗

PubMed1989

Recirculation of lymphocyte subsets (CD5+, CD4+, CD8+, T19+ and B cells) through fetal lymph nodes.

The experiments reported in this paper examine the cell-surface phenotype (CD5, CD4, CD8, T19, MHC class II and sIg) and cell output of lymphocyte subsets circulating through a subcutaneous lymph node in the sheep fetus, in an environment unaffected by foreign antigen and circulating immunoglobulins. CD4+ lymphocytes were the major T-cell subset in fetal lymph and were clearly enriched in lymph compared with blood, whereas T19+, CD8+ and B lymphocytes were not. It seems likely that in the fetus CD4+ lymphocytes are extracted from the blood at a faster rate than are other T-cell subsets and B cells. There was a much higher percentage of CD8+ and T null cells and a lower percentage of MHC class II+ and B cells circulating in the fetal lymph than in adult lymph, while the percentage of T19+ lymphocytes in fetal blood was twice that in the adult. Although the hourly cell output from an adult prescapular lymph node was far higher than that from a fetal lymph node, the circulation of lymphocytes through fetal lymph nodes was much greater per gram lymph node weight than that through adult lymph nodes. The wholesale recirculation in the fetus of all the major T-cell subsets found in the adult is paradoxical because it is not known what function they serve in the fetus in the absence of antigen and ongoing immune responses, although clearly they are not memory cells.

Animals↗

PubMed1988

CD4+ lymphocytes are extracted from blood by peripheral lymph nodes at different rates from other T cell subsets and B cells.

The circulation of lymphocyte subsets through prescapular lymph nodes in sheep has been quantified using a panel of monoclonal antibodies against sheep lymphocyte surface antigens. Differences in the extraction of lymphocyte subsets from blood by the lymph node were found with CD4+ lymphocytes being extracted at a faster rate (1/2) than CD8+, SBU-T19+, major histocompatibility complex class II+ and B cells (1/4 to 1/5). In order to accommodate existing data on organ-specific adhesion molecules, one subset specific and one tissue specific, expressed on vascular endothelium could act jointly to regulate the migration of recirculating lymphocytes.

Animals↗