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R Aspinall

Publications and source records attributed to R Aspinall.

At least 37 records · Page 2Linked to original sources
PubMed1998

Age-related changes in the absolute number of CD95 positive cells in T cell subsets in the blood.

Comparison of the absolute number of cells in distinct T cells subsets expressing CD95 (Fas) was carried out in two populations of healthy female volunteers. In one population, the average age was 30 +/- 5 years, and in the second population the average age was 73 +/- 13 years. No significant difference was noted in the total number of lymphocytes, CD3+, CD4+, or CD8+ cells per microL of blood between the two age groups, but major differences were noted in the number of cells expressing CD95. A significant reduction was seen in the number of cells per microL of blood in both the CD4+ CD45RA+ CD95+ and CD8+ CD45RA+ CD95+ populations in the older group compared with the younger group. Within the memory pool significantly fewer CD8+ CD45RO+ CD95+ cells were found in the older population compared with the younger group. No such difference were found in the number of CD4+ CD45RO+ CD95+ cells between groups. Such a significant decline in the number of CD95+ cells, whose expression is known to be linked with activation, may be implicated as a mechanism by which cells that have reached a stage of replicative senescence remain in the peripheral T cell pool. Anti-CD3-mediated activation of cells from both groups revealed much lower proliferative responses from the older group, supporting the idea that there is an age-associated increase in the number of cells that have reached their replicative limit. These cells may not be lost from the peripheral pool because they fail to express CD95.

Adult↗
PubMed1997

Age-associated thymic atrophy in the mouse is due to a deficiency affecting rearrangement of the TCR during intrathymic T cell development.

Involution of the thymus is a feature of age and precedes inefficient functioning of the immune system. C57BL/10 mice show an 83% reduction in number of thymocytes between 3 and 20 mo of age, with a significant decline in each of the thymic subsets defined by their expression of CD4 and CD8. The similar percentage contribution of each subset to the whole at 3, 12, and 20 mo suggests a lesion in the T cell developmental pathway within an early subset. The CD3- CD4- CD8- subset showed a significant decline in number by 20 mo of age, but despite this reduction, no significant difference was noted in the number of CD44+ CD25- cells, the earliest stage of this subset between 3 and 20 mo of age. A significant decline in the number of their progeny, the CD44+ CD25+, and the progeny of these cells, the CD44- CD25+ cells, was noted by 12 mo of age. Expression of CD25 within this subset is associated with rearrangement of TCR beta-chain genes. F5 transgenic mice, carrying a complete TCR-alphabeta transgene under the control of a CD2 minigene cassette on a C57BL/10 background, showed no age-associated thymic atrophy in any of the defined thymic subsets over the same period as the normal C57BL/10 mice. Similar results were noted with mice carrying the same transgene but which in addition were also RAG-1-. The results indicate that age-associated thymic involution was associated with problems with rearrangement of the TCR beta-chain genes affecting the production of thymocytes.

Aging↗
PubMed1997

Post-thymic T-cell development in the rat.

The presence or absence of CD4, CD8, Thy-1, RT6 and CD45RC revealed a number of T-cell subpopulations in the rat. Vascular thymus transplantation was used in RT7 congenics to establish the lineage relationship between these subpopulations by following phenotypic changes after thymus emigration. We found that recent thymic emigrants exhibit the Thy-1+/RT6-/CD45RC- phenotype and express either CD4 or CD8. Within 11 days after emigration, these cells differentiated into Thy-1-/RT6+/CD45RC+ cells. From 33 to 76 days following transplantation, a proportion of the latter lost RT6 and/or CD45RC expression, suggesting further differentiation. The pathway of 'mature' T-cell differentiation could be reconstructed from these data and analysis of the differences between T-cell subsets in thymectomized and normal control rats. End-stages of post-thymic T-cell differentiation in the rat were most likely to be Thy-1-/RT6+/CD45RC- and Thy-1-/RT6-/CD45RC+ T cells.

Aging↗
PubMed1996

A potential mechanism of action of an antibody (HIS45) which has been shown to induce prolonged graft survival.

Animals treated with the antibody HIS45 According to a regimen known to prolong the survival of allogenic skin grafts (1), show no significant decrease in alpha beta + T cells from their lymph nodes and no dramatic change in the levels of either alpha beta + CD4+ or alpha beta + CD8+ cells compared with untreated controls. However, the T cells of treated animals showed reduced expression of the alpha beta form of the T cell receptor. Although treatment did not lead to an upregulation of the CD25 molecule on the rat cells, treatment does lead to a reduction at the cell surface in the amount of the determinant recognized by HIS45. In vitro analysis revealed that the HIS45 determinant was lost from T cells following their activation but re-expressed later. The T cells in treated animals may be partially activated. This ability of HIS45 to partially activate cell was supported by experiments which revealed that the antibody HIS45 was only weakly mitogenic in vitro, but when present in conjunction with another stimulus such as anti-V beta cell receptor antibody or a mitogen or a superantigen, the HIS45 antibody was shown to produce significantly increased proliferation. Functional analysis of cells from treated animals showed they respond significantly less well in vitro to either superantigen (TSST-1) or alloantigen, compared to cells from age and sex matched untreated controls. Since no T cell depletion occurred following treatment the reduced functional ability of these cells must have been due to a functional defect in their ability to respond. The results suggest that HIS45 was having its immunosuppressive effect by delivering an incomplete activation signal to T cells leading to a state of anergy.

Animals↗
PubMed1995

gp120-induced programmed cell death in recently activated T cells without subsequent ligation of the T cell receptor.

In most individuals, HIV infection is characterized by a progressive decline in the number of peripheral blood CD4+ T lymphocytes, and while the number of CD4+ cells is within the normal range, defects in immune function are detectable. To date neither the decline in function nor the decline in cell number have been satisfactorily explained. Here we describe a mechanism which may contribute to the immunodeficiency and decline in CD4+ cell numbers in HIV-infected individuals. We show that recently activated T cells are susceptible to apoptosis when exposed to HIV gp120 in the presence of anti-gp120 antibody.

Antibodies↗
PubMed1994

Climate change impact on distribution and abundance of wildlife species: an analytical approach using GIS.

An analytical approach to modelling the likely impact of climate change on the distribution and abundance of wildlife species is described using examples from Scotland. Data for present day distribution of wildlife and habitat are analysed using map data describing geographic variation in climatic factors. Climate data for the present day and under specified scenarios of change are themselves modelled within a GIS; climate modelling uses meteorological station data, climate change scenarios developed from GCMs and a variety of spatial interpolation techniques. The analytical procedure generates hypotheses defining ecological relationships between species distribution and climatic factors (monthly, seasonal and annual data). These relationships are then used to model the distribution of the species directly from climate and predict impacts of climate change. The analysis takes account of both direct impacts of climate on wildlife and indirect effects manifested through habitat response to climate change. The analytical procedure is implemented as a generic tool for inductive spatial analysis in GIS.

Journal Article↗
PubMed1991

Prolonged survival of skin grafts following treatment with an antibody to a putative cell triggering molecule, QCA-1.

The QCA-1 molecule (quiescent cell antigen-1) appears to be involved in the differentiation events undergone by T cell following occupancy of the antigen receptor. Here we show that modulation of the QCA-1 antigen from the surface of the cell normally follows activation, and that treatment of animals with the antibodies against the QCA-1 molecule inhibits the normal response to an allograft without appearing to alter the number of peripheral T cells or the expression by these cells of the alpha/beta T cell antigen receptor.

Animals↗
PubMed1991

T-cell development in the fetus and the invariant series hypothesis.

Comparison of the timing of appearance of certain T-cell markers in the intrathymic development of T cells during gestation reveals a common sequence of expression in several species. Here Richard Aspinall and colleagues put forward a hypothesis concerning this 'invariant series' of markers that shares the same timing of expression across species barriers. It is proposed that T-cell markers that are members of the invariant series are very important in deciding the fate of a developing thymocyte.

Animals↗
PubMed1991

Induction of long-term survival of hamster heart xenografts in rats.

The aim of this study was to determine the mechanisms responsible for concordant xenograft rejection using the hamster-to-rat heart graft model. Even though it was known that rat CD4 positive T cells proliferated to hamster stimulators in mixed lymphocyte reactions, the depletion of CD4 positive T cells in rat recipients did not lead to an extension of xenograft survival. Suppression of T cell immunity using other monoclonal antibodies or cyclosporine also failed to improve survival. Only by depleting complement with cobra-venom factor could hamster xenograft survival be prolonged, and long-term survival was achieved by combining CsA with COF. High-antibody titers to hamster cells were found after transplantation of hamster hearts, and evidence is presented that rejection of these "concordant" xenografts is mediated primarily by antibody-complement mechanisms. The antihamster antibodies were produced in the absence of T cell help, which suggests that antibody-mediated graft destruction cannot be inhibited by suppression or depletion of T cells. Pharmacologic depletion of complement for the clinical application of concordant xenografts is a promising avenue of future research.

Animals↗
PubMed1990

Differences in turnover between thymic medullary dendritic cells and a subset of cortical macrophages.

To investigate the turnover of thymic accessory cells, we performed vascular thymus transplantation in RT7 congenic rats. mAb specific for one of the two allelic variants of the RT7 molecule, as well as mAb specific for either medullary interdigitating cells or a subset of cortical macrophages (M phi), were used on cryostat sections and cell suspensions prepared from grafted thymuses to monitor the turnover of these two cell types. In contrast to the complete turnover of interdigitating cells within 3 wk after transplantation, ED2-labeled cortical M phi showed a very slow turnover. Seventy-six days after transplantation, more than 30% of these M phi were found to be still of donor origin. The different turnover rates of these thymic accessory cells could reflect their function in T cell development.

Animals↗
PubMed1990

Inhibition of T cell responses in vitro by an antibody against a novel lymphocyte surface molecule (QCA-1).

We have identified an antigen present on the surface of lymphocytes in the rat which appears to play an important role in the preliminary stages of the immune response. This antigen, which we have called quiescent cell antigen 1 because of its apparent expression only on quiescent cells, is present on the majority of peripheral T and B cells and a small percentage of thymocytes which are located mainly in the medullary region. SDS-PAGE analysis of membrane molecules shows two bands on unreduced gels at approximately 43 and 47 kd. On reduction the bands ran at approximately 46 and 60 kd. When a monoclonal antibody against this antigen (HIS45) is present in an allogeneic mixed leukocyte reaction, it inhibits the proliferation of responding cells completely. When the antibody HIS45 is added to cytotoxic T lymphocyte mediated lysis assays it does not inhibit lysis nor does it affect the specificity of this lysis. Comparison with other antibodies which have been reported to affect lymphocyte function in rats and in other species fail to reveal any which have similar properties.

Animals↗
PubMed1990

In vitro and in vivo effects of monoclonal antibodies against T cell subsets on allogeneic and xenogeneic responses in the rat.

The Syrian hamster-to-rat represents an example of a concordant species difference, and therefore organ transplants using the hamster as the donor and the rat as the recipient are not rejected hyperacutely, as in discordant species combinations. Cellular mechanisms of xenogeneic rejection of hamster hearts by rats were studied both in vitro and in vivo, using monoclonal antibodies to rat T cell antigens. The results of this study reveal that CD4-positive cells of rats proliferated in vitro to both allogeneic stimulators and xenogeneic stimulators from a concordant strain, but required accessory cells of the responder phenotype to proliferate to discordant human stimulators. Monoclonal antibody therapy was used to prevent graft rejection in allogeneic and xenogeneic species combinations, using the rat as the recipient. Treatment with anti-CD4 antibodies was effective in prolonging allograft survival across a full MHC mismatch. No rejection occurred during antibody therapy, and long-term graft survival was achieved in 1/3 of transplanted grafts. The same monoclonal antibody therapy led to increased survival of grafts from hamster donors, but all of these grafts were rejected during therapy, and no long-term graft survival was achieved. Anti-CD8 antibody therapy, combined with anti-CD4 did not improve survival of hamster hearts in rats. Addition of cyclosporine to the anti-CD4 regimen also did not improve graft survival. Injection of an anti-T cell receptor antibody was no better than the anti-CD4 antibody in prolonging the survival times of heart grafts from the concordant xenogeneic species. These data suggest that the rejection of concordant xenogeneic tissue is not wholly a T cell-dependent phenomenon.

Animals↗
PubMed1990

RT7-defined alloantigens in rats are part of the leucocyte common antigen family.

Haemopoietic cells carry a variety of cell-surface molecules, some of which are known to have allotypic variation. In rats, the RT7 alloantigenic system has been well documented using alloantisera. We have produced the first mouse hybridoma cell line secreting an antibody, HIS41, which binds to leucocytes of rat strains carrying the RT7.2 but not the RT7.1 determinant. An IgG2b isotype switch variant (HIS41.2b) of the original HIS41 (IgG1 isotype) was also made. HIS41 showed a clear and discrete binding in immunofluorescent and histological experiments and has already been used in several studies on haemopoietic cell turnover and differentiation employing PVG rats congenic for RT7. The present study addresses the question of whether the RT7 gene products are members of the L-CA family, which has been a matter of controversy over the last decade. When using HIS41 for the analysis of tissue distribution and molecular weight of RT7 gene products, a strong similarity was evident with the data reported for the L-CA detected by MRC OX-1 and MRC OX-30. These two MoAb have been reported to bind to all members of the L-CA family. All haemopoietic cells, excluding erythrocytes and the more mature stages of erythropoiesis, stained with HIS41. The molecular weights of HIS41 binding molecules on thymocytes and peripheral T cells were comparable to the L-CA precipitated by MRC OX-1. Capping and sequential immunoprecipitation studies indicated that HIS41 and MRC OX-30-binding molecules were identical. MRC OX-1, however, appeared to bind only a subset of these molecules. Thus, our study confirms the identity of RT7.2 gene products and L-CA. It also revealed a difference between MRC OX-1 and MRC OX-30 not noticed previously.

Animals↗
PubMed1989

A monoclonal antibody to a determinant of the rat T cell antigen receptor expressed by a minor subset of T cells.

A hybridoma producing the monoclonal antibody HIS42 was isolated from a fusion between spleen cells from a BALB/c mouse immunized with rat thymocytes and the fusion partner SP2/0. This antibody recognizes a minor subset of T cells in every haplotype of rat tested so far. The subpopulation of HIS42 positive T cells contains both CD4+ and CD8+ cells, in the same ratio as found in the peripheral T cell population. When bound to Sepharose beads, HIS42 induces T cell proliferation in the presence of interleukin-2. In contrast to lymph node T cells, a number of thymocytes were found to express HIS42 only in the cytoplasm or together with membrane expression. Most bright HIS42 surface labelled thymocytes were also positive for MRC OX-44, a marker predominantly identifying mature thymocytes. SDS-PAGE analyses of the membrane molecules immunoprecipitated by HIS42 show two bands on unreduced gels. One of these bands (85 kd) runs as two separate bands at 35 and 48 kd on reduction. The other much weaker broad band (approximately 100 kd) is hardly affected by reduced conditions. Taken together these data suggest that HIS42 is directed against a determinant on the rat T cell receptor for antigen, which is common to a small number of T cells.

Animals↗
PubMed1989

A novel lymphocyte surface antigen recognized by the monoclonal antibody HIS45.

A hybridoma producing the monoclonal antibody HIS45 was isolated from a fusion between spleen cells from a Balb/c mouse immunized with rat bone marrow cells and the fusion partner SP2/0. This antibody recognizes a determinant present on the majority of peripheral T and B cells and a small percentage of thymocytes. In a xenogeneic mixed leucocyte reaction HIS45 completely inhibits the proliferation of responding cells. HIS45 does not inhibit natural killer cell-mediated lysis. Comparison with other antibodies which have been reported to effect lymphocyte function fail to reveal any which have similar properties.

Animals↗