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Biomedical subjects

W K Silvers

Publications and source records attributed to W K Silvers.

At least 55 records · Page 3Linked to original sources
PubMed1985

The influence of T-lymphocyte precursor cells and thymus grafts on the cellular immunodeficiencies of the BB rat.

To determine whether abnormal T-lymphocyte precursor cells or an abnormal thymus is responsible for the immunologic deficiencies of spontaneously diabetic BB rats, thymus grafts or T-cell-depleted bone marrow cells were exchanged between diabetes-prone and non-diabetes-prone animals. Analysis of peripheral lymphocyte populations from these recipients with monoclonal antibodies, a fluorescence activated cell sorter, and mixed lymphocyte culture tests indicate that an abnormal thymus is not responsible for the immunodeficiency of BB rats, but that the defect resides within the lymphocyte precursor pool.

Animals↗
PubMed1985

"Activated" T-lymphocyte levels in the spontaneously diabetic BB rat syndrome.

About 50% of individual members of a diabetes-prone stock of BB rats eventually become hyperglycemic (usually between 60 and 180 days of age) while the remainder remain normoglycemic for life. Circulating levels of Ia antigen bearing T-lymphocytes from different lymphoid compartments of acutely diabetic and normoglycemic (but diabetes prone) BB rats were determined with monoclonal antibodies in an effort to analyze the temporal relationship between levels of this unusual T cell antigen and the onset of diabetes. In young normoglycemic rats elevated blood levels of Ia-positive T-lymphocytes (greater than or equal to 4.00%) predicted the future development of hyperglycemia with a sensitivity of 85% and a specificity of 83%. The interval between the identification of these elevated levels and the onset of diabetes ranged from 22 to 82 days. After the development of hyperglycemia the level of Ia-positive T-lymphocytes declined progressively in all lymphoid compartments with chronicity of the diabetes. We conclude that Ia antigens bearing T cells serve as immunologic "markers" of susceptibility to diabetes in this "high-risk" population and probably reflect an ongoing immune process during the prediabetic state. Similar findings in humans with a family history of diabetes might lead to identification of prediabetic individuals and allow selective use of immunomodulation to prevent the disease.

Acute Disease↗
PubMed1985

Increased incidence of Ia antigen-bearing T lymphocytes in the spontaneously diabetic BB rat.

The frequency of Ia-positive T lymphocytes in spontaneously diabetic BB rats was assessed by using monoclonal antibodies and a fluorescence-activated cell sorter. These cells peaked in frequency during the early stages of hyperglycemia, with a gradual decline toward normal as the disease progressed. Significantly increased numbers of Ia-positive T cells were detected in both helper (W3/25+) and cytotoxic-suppressor (OX8+) subsets. The elevated levels of Ia-positive T lymphocytes in these rats may be relevant to the immune destruction of their beta cells.

Acute Disease↗
PubMed1984

Major histocompatibility complex restriction and transplantation immunity. A possible solution to the allograft problem.

Studies of the survival of weakly histoincompatible skin grafts in which the Langerhans' cells (LC)5 have been replaced with major histocompatibility complex (MHC)-compatible or incompatible LC, as well as studies of the fate of cultured endocrine allografts in MHC-compatible and incompatible mice and rats, indicate that allografts are only recognized as foreign if they possess donor macrophages (or cells of this family), or if antigen presenting cells MHC-compatible with the graft can be provided by the host.

Animals↗
PubMed1983

Influence of size and gene dosage on the survival of skin allografts on rats rendered tolerant at birth.

The attributes of the test grafts with which putatively tolerant rats are challenged influence their immune response. Lewis (Lew) rats inoculated at birth with Lew/BN F1 hybrid bone marrow cells accept large skin allografts more readily than small allografts, and F1 hybrid skin grafts survive better than BN transplants. The results indicate that the survivals of these major histocompatibility complex-incompatible grafts are determined by the same factors that operate when only weak histoincompatibilities prevail.

Animals↗
PubMed1983

Influence of islet and bone marrow transplantation on the diabetes and immunodeficiency of BB rats.

The results of islet transplantation in spontaneous autoimmune diabetes of BB rats were studied to determine whether this disease process might damage the transplanted islet tissue. Since BB rats are not genetically uniform, syngenetic grafts could not be used; therefore, allograft rejection was prevented by rendering BB rats immunologically tolerant of WF transplantation antigens by neonatal inoculation with bone marrow cells. Despite the resultant tolerant state, which permitted successful engraftment of WF skin allografts, the transplanted islets ameliorated the spontaneous diabetes of BB rats only briefly before they were destroyed by immune insulitis. BB rats from the diabetic stock were found to suffer from abnormalities in T lymphocytes and their subsets as well as defective immune response patterns. When analyzed with monoclonal antibodies specific for rat lymphocyte markers, BB rats of the diabetic stock were found to be lymphocytopenic. There was a reduction in helper T cells and a more severe deficit in the suppressor/cytotoxic subset. BB rats that were inoculated neonatally with bone marrow from normal donors were found to have a strikingly reduced incidence of diabetes. Moreover, the T cell functional, numerical, and microenvironmental defects that were present in noninoculated BB rats were restored in marrow-inoculated BB rats, findings possibly related to the decreased incidence of diabetes.

Animals↗
PubMed1983

Influence of culturing on the functioning of major-histocompatibility-complex-compatible and incompatible islet grafts in diabetic mice.

Culturing B10.BR (H-2k) islets promotes their survival in major histocompatibility complex (MHC)-incompatible BALB/c (H-2d) mice, but not in MHC-compatible CBA (H-2k) animals. These results provide further evidence that MHC restriction is involved in transplantation immunity--i.e., that allografts are only recognized as foreign if they possess donor macrophages (or cells of this family), or if antigen-presenting cells MHC-compatible with the graft can be provided by the host.

Animals↗
PubMed1983

Influence of Langerhans cells on the survival of H-Y incompatible skin grafts in rats.

Evidence is presented that Langerhans cells (LCs) play an important role in the rejection of H-Y incompatible skin grafts in BN rats. Not only are small male trunk skin isografts much more likely to be rejected by BN females than similarly sized male foot pad, tail, and ear skin transplants, all of which possess fewer LCs than trunk skin, but the survival of male trunk skin grafts can be prolonged by replacing their LC population with allogeneic female cells.

Animals↗
PubMed1983

Analytical and functional studies on the T cells of untreated and immunologically tolerant diabetes-prone BB rats.

Lymphocyte profiles of untreated diabetes-prone BB rats (BBDP) and their normal marrow-inoculated tolerant littermates were determined with the aid of a fluorescence-activated cell sorter by using monoclonal antibodies specific for rat T cell (W3/13) and T cell subsets (W3/25, T helper; OX8, T cytotoxic/suppressor). In contrast to non-diabetes-prone rats and to their marrow-inoculated littermates, untreated BBDP rats were found to be T lymphocytopenic with reduced W3/25+ cells and with a major loss of OX8+ cells. Moreover, their lymphocytes displayed depressed alloreactivity that was not restored by addition of exogenous IL 2.

Animals↗
PubMed1983

Numerical and functional abnormaLity of T suppressor cells in diabetic rats.

Insulin-dependent diabetic patients have been reported to have abnormal suppressor T cell function. However, the importance of this abnormality in the etiology of the disease is difficult to evaluate, since the abnormality could be a result of hyperglycemia rather than a predisposing factor. A genetic condition in rats that closely resembles type I (insulin-dependent) diabetes mellitus made it possible to study their suppressor T cell status before they displayed the disease. Thus, monoclonal antibodies and a fluorescence-activated cell sorter were used to define lymphocyte subpopulations in these animals. In prediabetic rats the number of suppressor T cells was reduced strikingly. In vitro assays showed that lymphocytes from predisposed rats were also functionally deficient in regard to suppression. Susceptible rats inoculated with bone marrow cells from normal donors were protected from diabetes. Moreover, the numbers and functions of suppressor T cells in these marrow recipients were almost restored to normal. These observations indicate that a suppressor T cell abnormality is responsible for the hyperglycemia of diabetic rats and raises the possibility that the human disease has a similar etiology.

Animals↗
PubMed1982

Failure of host axons to regenerate through a once successful but later rejected long nerve allograft.

Host axons will regenerate through a long nerve allograft in an immunologically tolerant rat. However, if tolerance is abolished, rejection occurs and allogeneic cells (e.g., Schwann, vascular, perineurial, etc.) as well as regenerated host axons disappear from the allograft. Because following tolerance abolition host axons begin to regenerate into the connective tissue remnants of the rejected nerve allografts, the extent of this renewed axonal growth was investigated. It was found that in a tolerance-abolished rat, host axons only regrew in to the proximal 1 cm of a 4-cm allograft which in a fully tolerant recipient would have had numerous allogeneic Schwann cell-myelinated axons throughout its length. It is concluded that viable allogenic cells (i.e., Schwann, fibroblast, and vascular) together with their connective tissue matrix provide the best way to aid host nerve fiber regeneration through a long nerve allograft.

Animals↗
PubMed1982

Spontaneous diabetes in BB rats: evidence for a T cell dependent immune response defect.

Approximately 50% of BB rats develop insulinopenic hyperglycaemia and ketosis spontaneously in association with insulitis. Amelioration of the syndrome by immunosuppression suggests a cell mediated immune pathogenesis. Analysis of the cell-mediated immune profile of overtly diabetic and normoglycaemic diabetes prone BB rats indicates that they are lymphocytopenic relative to non-diabetes prone BB rats and that the T cell pool is particularly affected. Furthermore, lymphocytes from diabetic and diabetes prone BB rats, while producing normal responses to the T cell mitogen concanavalin A, do not respond when mixed in vitro with major histocompatibility complex incompatible lymphocytes. This anergy is not restored either by enriching the responding cell population for T cells or by adding exogenous T cell growth promoting factor. Thus BB rats have a numerical and regulatory deficit of their T cells which could be related to their propensity for diabetes.

Animals↗