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H M Georgiou

Publications and source records attributed to H M Georgiou.

At least 37 records · Page 2Linked to original sources
PubMed1994

Lymphocyte subsets in thymus and peripheral lymphoid tissues of aging and diabetic NOD mice.

The nonobese diabetic (NOD) mouse spontaneously develops insulin dependent diabetes mellitus. The disease is associated with a leucocytic infiltration of the pancreatic islets of Langerhans and it is believed that during the development of autoimmune diabetes, the insulin-secreting islet beta-cells are destroyed by autoreactive T lymphocytes. We investigated the alteration of lymphocyte subsets in central and peripheral lymphoid organs of NOD female mice with increasing age beginning before the onset of insulitis and ending well after the onset of diabetes. The spleen, inguinal and pancreatic lymph nodes all increased in cell number, especially after the onset of insulitis (8 weeks), and all decreased after the onset of diabetes. Flow cytometric studies showed a widening of the visible side scatter profile of female NOD lymph node cells which coincided with the initiation of insulitis. Anti-CD4 and anti-CD8 double staining of thymocytes revealed a large increase in the double negative population and a corresponding decrease in the double positive population, but this occurred long after the onset of diabetes. Generally, there was an increase in the CD4:CD8 ratio in the peripheral lymphoid organs during the onset of insulitis which was largely due to an increase in the CD4 T cell population while the ratio decreased after the onset of diabetes. In the spleen this was mostly due to an increase in CD8 T cells. The pancreatic lymph nodes, which theoretically might reflect what is happening in the pancreas, showed an unexpected decrease in overall cell number and a decrease in T-cells (especially CD4 T cells), while B cells were increased.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1993

The effect of cyclophosphamide treatment on lymphocyte subsets in the nonobese diabetic mouse: a comparison of various lymphoid organs.

The nonobese diabetic (NOD) mouse is a model for human Type 1 diabetes mellitus. Pancreatic beta-cell destruction in NOD mice is mediated by an autoimmune process which can be accelerated by cyclophosphamide (CP). We studied the phenotype of lymphocytes from central, peripheral and regional lymphoid tissues in prediabetic NOD and C3H mice before and after a single large dose of CP. All lymphoid organs showed a greatly diminished cell number and most alterations appeared early after CP and were transient, but an aggressive insulitis was not seen in NOD mice until 14 d after injection. The pancreatic islets in C3H mice remained intact and were not infiltrated. NOD female mice, which are most prone to spontaneous and CP-induced diabetes, exhibited the most unusual lymphoid kinetics after treatment with CP. Their thymus and spleen showed the least relative drop in total cell number and the most rapid rate of recovery. The thymus of these mice was also found to have an increased proportion of CD3+ thymocytes while CD4/CD8 double positive thymocytes decreased 7 d after CP. At 14 d after CP the number of IL-2R+ thymocytes had surpassed that of normal levels. The most dramatic observation was the rapid recovery and overshoot in the number of pancreatic lymph node cells of female NOD mice which coincided with aggressive insulitis.

Animals↗
PubMed1989

Thymus transplantation and disease prevention in the diabetes-prone Bio-Breeding rat.

Bio-Breeding rat T lymphocytes proliferate poorly in response to alloantigen. Transplantation of Bio-Breeding rats with fetal thymus tissue from diabetes resistant rats leads to an improvement in the T cell proliferative response, but only if the thymus contains bone marrow-derived, radiation-resistant thymic antigen presenting cells of the diabetes-resistant phenotype. The current study provides evidence that thymus transplantation leading to the restoration of Bio-Breeding T cell proliferative function can also significantly reduce the incidence of insulitis and prevent the development of diabetes. It appears that a defect in the bone marrow-derived thymic APC population contributes to an abnormal maturation of Bio-Breeding T lymphocytes which in turn predisposes animals to insulitis and diabetic disease.

Animals↗
PubMed1989

Persistent immunogenicity of rat thymic epithelium.

Culture of thymus tissue in 2-deoxyguanosine (2dGua) is thought to reduce tissue immunogenicity by selectively depleting highly immunogenic, thymic migrants of bone marrow origin. In the mouse 2dGua-treated thymus tissue survival is markedly enhanced compared with untreated tissue when transplanted under the kidney capsule of allogeneic recipients. These experiments were repeated in a rat model. As expected, DA strain neonatal thymus tissue was rejected when transplanted under the kidney capsule of normal allogeneic strain PVG rats. Surprisingly, acute rejection occurred when the tissue was cultured in 4 mM 2dGua, a dose capable of destroying rat thymocytes in vitro and 3 times the effective dose in mice. To test whether residual marrow-derived cells that escaped 2dGua treatment were responsible for inducing rejection, the treated DA tissue was "parked" in T cell-depleted PVG rats. Our working hypothesis was that the few remaining donor-derived cells of marrow origin would be overgrown by host-type cells. When 2dGua-treated DA thymus tissue was transplanted into T cell-depleted PVG recipients rejection did not occur. However this DA tissue, parked for as long as 200 days in T cell-depleted rats, was acutely rejected when retransplanted into normal PVG recipients. These results suggest that rat thymic epithelium devoid of marrow-derived cells in innately immunogenic.

Animals↗
PubMed1988

T cell dysfunction in the diabetes-prone BB rat. A role for thymic migrants that are not T cell precursors.

Diabetes-prone BB (BB-DP) rats express several T cell dysfunctions which include poor proliferative and cytotoxic responses to alloantigen. The goal of this study was to determine the origin of these T cell dysfunctions. When BB-DP rats were thymectomized, T cell depleted, and transplanted with neonatal thymus tissue from diabetes-resistant and otherwise normal DA/BB F1 rats, the early restoration of T cell function proceeded normally on a cell-for-cell basis; i.e., peripheral T cells functioned like those from the thymus donor. Because the thymus in these experiments was subjected to gamma irradiation before transplantation and there was no evidence of F1 chimerism in the transplanted BB-DP rats, it appeared that the BB-DP T cell precursors could mature into normally functioning T cells if the maturation process occurred in a normal thymus. If the F1 thymus tissue was treated with dGua before transplantation, the T cells of these animals functioned poorly like those from untreated BB-DP rats. dGua poisons bone marrow-derived cells, including gamma radiation-resistant cells of the macrophage/dendritic cell lineages, while sparing the thymic epithelium. Therefore, the reversal of the T cell dysfunction depends on the presence in the F1 thymus of gamma radiation-resistant, dGua-sensitive F1 cells. Conversely, thymectomized and T cell-depleted F1 rats expressed T cell dysfunction when transplanted with gamma-irradiated BB thymus grafts. T cell responses were normal in animals transplanted with dGua-treated BB thymus grafts. With increasing time after thymus transplantation, T cells from all animals gradually expressed the functional phenotype of the bone marrow donor. Taken together these results suggest that BB-DP bone marrow-derived cells that are not T cell precursors influence the maturation environment in the thymus of otherwise normal BB-DP T cell precursors.

Animals↗
PubMed1988

A requirement for the CD5 antigen in T cell activation.

Treatment of adult rats with a monoclonal antibody specific for the CD5 antigen led to a dramatic reduction in the number of CD5+ cells. However, a substantial number of T cells remained as assessed by other T cell-specific antibodies. These CD5- T cells did not proliferate in response to alloantigen or mitogenic stimulation, did not generate cytotoxic T lymphocytes in vitro, and did not induce graft-vs.-host disease when injected into susceptible recipients in vivo. Re-expression of the CD5 antigen occurred when CD5- T cells were placed in an environment devoid of the anti-CD5 antibody. Re-expression of the antigen was followed by return of the T cell proliferative responses. While CD5- T cells could not proliferate in response to alloantigen they could produce interleukin 2 following a short pulse with the T cell mitogen concanavalin A. However, T cell proliferative or cytotoxic responses could not be rescued by the addition of an exogenous source of interleukin 2. We conclude that the CD5 antigen appears to be required for proliferation of resting T cells.

Animals↗
PubMed1984

Islet cell subpopulations in cultured mouse fetal pancreas and pancreatic isografts.

Application of the immunoperoxidase technique proved very rewarding in determining the structure and function of cultured fetal pancreas and isografted tissue. Proliferation of endocrine beta-cells was highest during the first three weeks of culture but these cells rapidly declined in number thereafter as the delta-cell mass increased. Morphologically, the optimal culture time, based on beta-cell mass, was approximately ten to 14 days and this did not appear to be dependent on whether the tissue was cultured under conventional or high oxygen conditions. It is hoped that electron microscopy may reveal the fate of the diminishing population of insulin-producing cells. Immunoperoxidase staining of long-term isografts demonstrated the presence of large islets with the typical morphologic structure of normal adult pancreatic islets. It is believed that this may be of vital importance if pancreatic islet transplantation is to be fully effective in the control of blood glucose levels, which it is hoped will help prevent the longterm diabetic complications associated with insulin-dependent diabetes.

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