Biomedical subjects

D L Greiner

Publications and source records attributed to D L Greiner.

At least 91 records · Page 5Linked to original sources

PubMed1994

Influence of gonadal steroids on susceptibility to Brugia malayi in scid mice.

In the present study, we demonstrate that male scid/scid mice have higher adult worm burdens than do female scid/scid mice following equal challenge doses of infective Brugia malayi L3 larvae. Gonadectomy of four week old immature mice has no effect on worm burden in either sex, suggesting that the gender dichotomy between males and females does not depend on continued presence of endogenous gonadal steroids. The worm yield from female, but not male, mice can be increased by prepubertal oophorectomy combined with administration of either estradiol or testosterone in depot form. Our results raise the possibility that prepubertal steroid pulse(s) result(s) in physiological changes in male scid/scid mice that enhance worm growth. These studies confirm earlier reports of epidemiological data in humans suggesting a sexual dimorphism in susceptibility to filarial infection. Our data suggest that this gender difference is not due simply to the presence of adult gonadal steroids, but rather to ontogenic differentiative actions of sex steroids in the host.

Animals↗

PubMed1994

Role of RT6+ T lymphocytes in mercury-induced renal autoimmunity: experimental manipulations of "susceptible" and "resistant" rats.

Brown Norway (BN) rats, "susceptible" to the autoimmune effects of mercury, experience a decrease of peripheral RT6.2+ T lymphocytes after the injection of relatively low doses of mercuric chloride. This change coincides with the appearance of circulating autoantibodies to renal antigens (e.g., laminin). Lewis (LEW) rats, "resistant" to the autoimmune effects of mercury, do not show significant decreases of RT6+ T cells. It is possible that BN rats are particularly sensitive to stress induced by mercury and that secretion of adrenocortical hormones decreases levels of RT6+ T cells in this rat strain. Alternatively, mercury may induce a graft-versus-host-like syndrome in BN rats, resulting in higher levels of corticosteroids capable of affecting RT6+ lymphocytes. To eliminate the possible influence of adrenocortical hormones, we have adrenalectomized BN rats prior to administration of mercury. Autoimmune responses to renal antigens were not affected by this experimental manipulation. Similarly, adrenalectomized rats exposed to mercury showed a significant decrease of RT6+ T lymphocytes in cervical lymph nodes. Overall, these observations do not support the hypothesis that increases in adrenocortical hormones play a major role in mercury-induced changes of RT6+ T cells. We have also explored whether experimental depletion of RT6+ T lymphocytes would result in autoimmunity. Gamma irradiation of BN rats led to a decrease of RT6+ T splenocytes, but by itself (i.e., without exposure to mercury) did not cause autoimmune responses to renal antigens. In addition, gamma-irradiated BN rats treated with mercury had autoimmune responses similar to those observed in mercury-treated nonirradiated controls. Depletion of RT6+ T cells in LEW rats through the use of a monoclonal antibody against the RT6.1 alloantigen did not by itself cause renal autoimmunity in this "resistant" strain. Depletion followed by administration of mercury also failed to induce renal autoimmunity. The lack of autoimmune effects in RT6-depleted BN and LEW rats suggests that a combination of several factors may be necessary to break self-tolerance and cause mercury-induced autoimmunity. Such factors likely comprise both environmental (mercury) and endogenous, genetically determined components. The latter include regulatory T cells (possibly RT6+), major histocompatibility complex (MHC), and T-cell receptors (TCR). Thus, BN rats with decreased percentages of immunoregulatory RT6+ T lymphocytes require additional immunotoxic and/or toxic effects of mercury for autoimmunity to occur. On the other hand, LEW rats depleted of regulatory T cells may still be unable to develop renal autoimmunity after exposure to mercury because they lack the appropriate MHC and TCR.

Adrenalectomy↗

PubMed1994

Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes.

The murine severe combined immunodeficiency (scid) mutation was used to assess whether the diabetogenic effects of multiple low-dose streptozocin (MD-STZ) administration required the presence of functional T-cells. An STZ dose as low as 30 mg/kg body wt for 5 days induced hyperglycemia in young NOD/Lt-+/+ male mice, whereas a dose of 50 mg/kg for 5 days was required to elicit comparable hyperglycemia in C.B.-17-+/+ male mice. The greater NOD strain sensitivity was not a function of preexisting insulitis, because insulitis- and diabetes-free NOD male mice congenic for a diabetes-resistant major histocompatibility complex haplotype were equally susceptible to MD-STZ. This was confirmed in NOD-scid/scid and C.B.-17-scid/scid males. Both were completely insulitis-free, and despite the absence of functional T- cells and B-cells, both congenic stocks were as sensitive to MD-STZ as congenic +/+ controls. Indeed, MD-STZ-induced hyperglycemia in NOD-scid/scid male mice was significantly higher than in NOD/Lt-+/+ male mice. The NOD-scid/scid mouse as a recipient of adoptively transferred splenocytes clearly delineated a distinct pathogenesis of spontaneous insulin-dependent diabetes mellitus (IDDM) versus MD-STZ-induced hyperglycemia. Splenocytes from spontaneously diabetic NOD/Lt males, but not those from donors given MD-STZ, readily transferred IDDM, even when host beta-cells were sensitized by a single injection of STZ before adoptive transfer. We conclude that IDDM induced by MD-STZ is not mediated by T-cell- or B-cell-dependent autoimmune mechanisms in a fashion analogous to the spontaneous IDDM characteristic of NOD mice.

Animals↗

PubMed1994

A selective culture system for generating terminal deoxynucleotidyl transferase-positive lymphoid precursor cells in vitro. IV. Properties and developmental relationships of the lymphoid cells in the adherent and nonadherent compartments of the culture.

In a selective culture system, the in vitro generation of terminal deoxynucleotidyl transferase positive (TdT+) B cell progenitors from rat, mouse, and human bone marrow (BM) is characterized by initial lymphoid colonization of a mouse BM feeder layer. In the present study, four sequentially appearing subsets of B cell progenitors in the culture system are characterized. The first lymphoid subsets to appear, and presumably the least mature, are the adherent TdT- and TdT+ cells that reach plateau numbers on days 3 and 7, respectively. The appearance of TdT+ cells in the adherent phase of the culture is closely followed by a parallel increase in the number of TdT+ cells in the nonadherent phase, suggesting the release of a constant proportion of the adherent lymphoid cells from the feeder layer. Lastly, a wave of TdT- lymphoid cells is observed in the nonadherent fraction. All of the lymphoid cells generated in the cultures expressed the rat equivalent of the B220 antigen, whereas only one-half of the lymphoid cells (and one-half of the TdT+ cells) expressed the heat stable antigen (HSA), while none expressed surface or cytoplasmic immunoglobulin (Ig). This phenotypic profile identifies one-half of the generated lymphoid cells as pre-pro-B cells and the remainder as early to late pro-B cells. It also demonstrates that TdT is initially expressed prior to HSA expression in rat B cell differentiation. In vitro transfer experiments demonstrate that virtually all the precursors of TdT+ lymphoid cells (pre-TdT cells) in rat BM adhere to the mouse BM feeder layer during the first 24 hours of culture, and by day 7 of culture, the total pre-TdT cell activity in the adherent cell compartment increases more than 20-fold on a per cell basis and more than 70-fold on a per well basis. Finally, it was observed that a decrease in the concentration of fetal bovine serum (FBS) in the culture medium resulted in the selective release of the adherent TdT+, but not TdT-, lymphoid cells into the nonadherent compartment. These studies indicated that a stepwise progression of the earliest detectable stages in lymphoid development was associated with changes in stromal cell/lymphoid cell interactions that were partly regulated by serum-dependent adhesion mechanisms.

Animals↗

PubMed1994

Thymic epithelial defects and predisposition to autoimmune disease in BB rats.

We report an association between thymic epithelial defects and predisposition to autoimmunity. Diabetes-prone (DP) BB rats develop spontaneous hyperglycemia and are deficient in T cell subsets expressing the RT6 alloantigen. Diabetes resistant (DR) BB rats become diabetic if depleted of RT6+ T cells. The inciting immune system defects are unknown. We made the following observations: 1) Regions of thymic cortex and medulla devoid of thymic epithelium exist in DP-BB, DR-BB, and Lewis rats, all of which are susceptible to autoimmune disorders. Such defects were absent in eight normal rat strains. 2) Thymic epithelial defects are absent at birth, but present in BB rats at 4 weeks of age. 3) The genetic predisposition to thymic epithelial defects is an autosomal dominant trait. 4) The observation of thymic defects in (DP x WF)F1 rats led to the prediction that such animals, which never develop spontaneous autoimmunity, might be susceptible to its induction. Following depletion of RT6+ T cells we observed diabetes in 91%, and thyroiditis in 43%, of treated F1 animals (n = 23). Pancreatic insulitis was uniformly present. Because thymic epithelium participates in the positive and negative selection of developing thymocytes, we propose that thymic epithelial defects may play an important role in the predisposition of BB rats to autoimmunity.

Aging↗

PubMed1993

The RT6 rat lymphocyte alloantigen circulates in soluble form.

RT6 is a rat maturational lymphocyte alloantigen that appears to subserve important immunoregulatory functions. The lymphopenic diabetes-prone BioBreeding (BB)/Worcester rat is severely deficient in RT6+ T cells and develops spontaneous autoimmune diabetes mellitus. Transfusion of RT6+ T cells prevents the disease. Conversely, in vivo immune elimination of RT6+ T cells from the diabetes-resistant line of BB rats induces diabetes and thyroiditis. RT6 protein is expressed in two allotypic forms, each linked to the cell surface by a phosphatidylinositol (PI) anchor. The mechanism by which RT6+ T cells exert their regulatory function is not known, nor is the function of the RT6 protein defined. In this study, we investigated the possibility that, like other PI-linked proteins, RT6 also exists in a soluble form in the circulation. Using standard biochemical procedures we observed: (i) Soluble RT6 circulates in readily detectable amounts in all rat strains studied. (ii) The diabetes-prone BB rat circulates less RT6.1 than does any other strain, including the coisogenic diabetes-resistant line. (iii) Injections of monoclonal anti-RT6.1 antibody rapidly eliminate soluble RT6 from the circulation of diabetes resistant BB rats. The existence of a soluble form of a protein associated with immunoregulatory T cells suggests the possibility that soluble RT6 itself might possess immunomodulatory properties.

ADP Ribose Transferases↗

PubMed1993

Relative susceptibility of SJL/J and B10.S mice to experimental allergic encephalomyelitis (EAE) is determined by the ability of prethymic cells in bone marrow to develop into EAE effector T cells.

SJL/J mice are highly susceptible to actively induced experimental allergic encephalomyelitis (EAE), whereas B10.S mice are resistant. However, both strains share the H-2s haplotype. We have previously shown that the relative susceptibility of SJL/J and B10.S mice to acute EAE correlates, respectively, with high and low responsiveness to myelin basic protein (MBP), as determined by cloning and limiting dilution analysis of in vitro T cell proliferation. Here, we have investigated the ability of SJL/J and B10.S mice to generate EAE-effector T cells in vivo. We have developed a new mouse strain, B10.S Thy 1.1, that differs at the Thy 1 locus from SJL/J and B10.S mice (both Thy 1.2) but has the same MHC and resistance pattern to EAE as do B10.S mice. Using radiation bone marrow chimeras formed between SJL/J and B10.S Thy 1.1 mice, we have shown that a population of radiosensitive prethymic cells in SJL/J bone marrow has an intrinsic potential to generate EAE-effector T cells, whereas that in B10.S Thy 1.1 bone marrow does not. This lack of detectable EAE effector cells in B10.S Thy 1.1 mice does not appear to be due to the generation of suppressor T cells or to a defect in antigen-presenting cells. Moreover, the potential of SJL/J bone marrow to generate EAE-effector T cells is not inhibited by the concomitant presence of B10.S Thy 1.1 bone marrow cells, thymocytes or dendritic cells in mixed chimeras. Hence, the relative susceptibility of SJL/J and B10.S mice to EAE appears to be directly related to the respective responder status of their T cells to MBP, as evidenced by their ability (or inability) to generate EAE-effector T cells. This high and low responder status appears in turn to be linked to non-MHC background genes, although this has not been established formally.

Animals↗

PubMed1993

Mercury-induced renal autoimmunity: changes in RT6+ T-lymphocytes of susceptible and resistant rats.

The repeated administration of mercury to rats of the Brown Norway (BN) inbred strain results in a self-limiting production of autoantibodies to renal antigens (e.g., laminin) and autoimmune glomerulonephritis. In contrast, rats of the Lewis (LEW) strain do not develop renal autoimmunity after mercury treatment. Suppressor T-cells and/or the idiotype-anti-idiotype network have been implicated in the control of autoimmunity in susceptible (BN) rats as well as the "resistant" state of nonsusceptible (LEW) animals. In our investigations of the immune regulation of mercury-induced autoimmune glomerulonephritis, we have performed a phenotypic analysis of lymphocyte subpopulation in the spleens and lymph nodes of mercury-treated and control LEW, BN, and (BN x LEW) F1 hybrid rats. Of particular interest were RT6+ T-cells, a subpopulation of lymphocytes that may have immunoregulatory properties and show a relative decrease in mercury-treated BN rats concomitantly with the development of autoimmune responses to renal autoantigens. LEW rats did not develop renal autoimmunity after mercury treatment and had no significant change in the ratio of RT6+ to RT6- T-lymphocytes. Interestingly, the administration of mercury to (BN x LEW) F1 hybrid rats caused effects similar to those observed in the BN strain. Auto-immune responses to antigens of the kidney coincided with a change in the balance within the RT6 cell population, which was altered in favor of T-lymphocytes that do not express the RT6 phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Animal models for immunodeficiency diseases.

Immunodeficient animals continue to provide insights into the development and function of the immune system. These animals also serve as models for the propagation of normal and malignant human cells and as hosts for infectious agents, including HIV. New developments in basic and applied research using immunodeficient animals were discussed at a recent workshop.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Lack of peripherally induced tolerance to established skin allografts in immunologically reconstituted scid mice.

The mechanism by which the antigen-specific immune system distinguishes between foreign antigens (toward which it mounts an immune response) and self-antigens (of which it is tolerant) is not completely understood. Studies using "superantigens" and transgenic mice have allowed investigations into some of the mechanisms of clonal deletion, anergy, and peripheral tolerance. In the present report, we have attempted to develop a new model system to investigate the possible mechanism(s) of peripheral tolerance to allografts. In this system, skin grafts from C57BL/6J (B6; H-2b) mice are grafted onto T- and B-lymphocyte-deficient C.B-17-scid/scid (H-2d; hereafter referred to as scid) mice. Because of their lack of functional lymphocytes, the scid mice readily accept the allogeneic skin grafts. After the allografts healed, the scid mice were reconstituted with T-cell-deficient fetal liver from coisogeneic C.B-17-+/+ mice or bone marrow from weanling congenitally athymic BALB/c-nu/nu (H-2d; hereafter referred to as nude) mice. Upon immunological reconstitution, the scid mice rejected the established B6 skin allografts, suggesting that an immune system developing in the presence of an intact peripheral skin allograft fails to develop tolerance to the peripheral allograft. This model system may be useful for the study of the mechanisms required for the induction of peripheral tolerance.

Animals↗

PubMed1992

Thymic involution in viable motheaten (me(v)) mice is associated with a loss of intrathymic precursor activity.

Mice homozygous for the viable motheaten (me(v)) allele manifest abnormalities in thymocytopoiesis, are severely immunodeficient, and develop autoimmune disorders early in life. Premature thymic involution occurs in me(v)/me(v) mice, and their bone marrow prothymocytes are unable to repopulate the thymus of adoptive recipients following intravenous (i.v.) transfer. However, analysis of thymocytopoiesis following intrathymic (i.t.) adoptive transfer of bone marrow from me(v)/me(v) mice demonstrates the presence of normal numbers of prothymocytes. To investigate intrathymic development in me(v)/me(v) mice, we determined intrathymic precursor cell number and activity. Dual labeling analyses showed that an involuted me(v)/me(v) thymus is relatively enriched (fivefold) in CD4-CD8- thymocytes (intrathymic precursor phenotype) compared with wild-type (+/+) thymus. However, thymocytes from me(v)/me(v) mice were deficient in precursor activity when adoptively transferred i.t. into irradiated recipients. Thymocytes recovered from the involuted thymus of aged or steroid-treated normal mice also displayed reduced precursor activity. However, the phenotypic profile of thymocyte subsets from steroid-treated mice was enriched in single positive cells (mature phenotype) and was distinctly different from the subset distribution of thymocytes in me(v)/me(v) and aged mice. These results suggest that intrathymic precursor activity in me(v)/me(v) mice is decreased, and may be reflective of decreased prothymocyte seeding to the thymus in vivo. In addition, the results suggest that the thymic involution in me(v)/me(v) mice is not due solely to effects of corticosteroids.

Animals↗

PubMed1992

Rat stem-cell factor induces splenocytes capable of regenerating the thymus.

Cytokine regulation of prethymic T-lymphoid progenitor-cell proliferation and/or differentiation has not been well-defined, although much is known of cytokine regulation of hemopoietic stem- and progenitor-cell development. Here we use a recently identified hemopoietic growth factor, stem-cell factor (SCF) (a form of the c-kit ligand), and a transplant model of thymocyte regeneration to assess the effect of SCF on the in vivo generation of prethymic, thymocyte progenitor-cell activity. We show that recombinant rat SCF (rrSCF164) administered to weanling rats selectively induces an increase in thymocyte progenitor activity in the spleens of treated rats as compared to rats treated with vehicle, polyethylene glycol (PEG)-conjugated rat albumin, or recombinant human granulocyte colony-stimulating factor (rhG-CSF). These data demonstrate that administration of SCF in vivo affects extrathymic-origin thymocyte regenerating cells and may influence, directly or indirectly, early prethymic stages of T-cell lymphopoiesis in addition to its known effect on early stages of myelopoiesis and erythropoiesis.

Animals↗

PubMed1992

CD8+ T lymphocytes are not required for murine resistance to human filarial parasites.

Mice are resistant to the establishment of infection with the nematode parasite Brugia malayi, an etiologic agent of human lymphatic filariasis. We have recently shown that T and B lymphocyte-deficient C.B.-17 scid/scid mice are permissive for infection with this parasite, whereas coisogenic C.B.-17+/+ mice are resistant. This observation suggests that T and B lymphocytes that comprise the antigen-specific immune system orchestrate murine resistance to B. malayi. In order to define the component of the antigen-specific immune response that is responsible for this resistance, we have tested the susceptibility of beta 2M-/- mice to infection with B. malayi L3 larvae. These mice are homozygous for insertional disruption of their B2m genes, which encode beta 2-microglobulin, the small subunit of the major histocompatibility (MHC) antigens. They do not express beta 2-microglobulin and, as a consequence, fail to express the class I major histocompatibility antigens, and they do not develop the CD8+ class I MHC-restricted cytotoxic T cell subset. We find that these mice are completely resistant to B. malayi, indicating that the CD8+ T lymphocyte subset is not an obligate requirement for murine resistance to human filarial parasites.

Animals↗

PubMed1992

Evidence for elevated prothymocyte activity in the bone marrow of New Zealand Black (NZB) mice. Elevated prothymocyte activity in NZB mice.

New Zealand Black (NZB) mice spontaneously develop an autoimmune syndrome similar to that of systemic lupus erythematosus. Numerous abnormalities in T lymphocyte development have been reported in NZB mice, and the autoimmune syndrome can be adoptively transferred to naive recipients using bone marrow cells. In the present study, we have used an adoptive transfer system to study quantitatively the relative prothymocyte activity of marrow in either young (4-6 weeks of age) or older (8-10 months of age) NZB mice. Our results demonstrate that NZB marrow has approximately 7-fold more prothymocyte activity than that of marrow in SEA mice, a histocompatible, non-autoimmune prone normal strain of mice. This was ascertained by a competitive repopulation assay, in which mixtures of NZB and SEA prothymocytes were compared directly for their ability to repopulate the thymus of adoptive recipients. This increase in prothymocyte activity in the primary recipient of NZB marrow was associated with an increased competitive advantage of NZB marrow prothymocytes over that of SEA marrow prothymocytes in repopulating the hemopoietic (bone marrow) compartment of the primary host. These findings suggest that elevated prothymocyte activity in NZB mice, along with our previously presented evidence for abnormalities of thymocytopoiesis in NZB mice, may be important in their predisposition for autoimmunity.

Animals↗

PubMed1992

Survival of Onchocerca volvulus in nodules implanted in immunodeficient rodents.

Onchocerca volvulus is an obligate human parasite, and its study has been difficult due to an inability to maintain it outside the human host. We report the successful transplantation of onchocercomata containing living adult O. volvulus worms into immunodeficient C.B.-17.scid/scid (scid) mice or athymic rnu/rnu (nude) rats. Living, motile worms containing viable microfilariae were present in onchocercomata recovered from scid mice or nude rats for up to 20 wk, establishing a novel animal model for future investigation of O. volvulus.

Animals↗

PubMed1991

The immunodeficient scid mouse as a model for human lymphatic filariasis.

The C.B.-17-scid/scid mouse (hereafter referred to as the scid mouse) is homozygous for a recessive mutation at a locus that influences the assembly of intact immunoglobulin and T cell receptor genes. Therefore, scid mice cannot generate functional B or T lymphocytes, are profoundly immunodeficient, and have been reported to be receptive to reconstitution with human immune cells. In the present study, we injected scid mice with infective larvae of the human filarial parasite Brugia malayi. Within 6-10 wk after subcutaneous injection of infective L3 larvae, both male and female worms were observed in various stages of development in 90% of the mice. In animals tested 8 weeks or more after infection, microfilariae were detected in the blood or peritoneal cavity of 52% of the mice examined. Adult worms were observed in the lymphatics of the infected scid mice, where their presence was associated with lymphangitis and lymphangiectasia. These results suggest that the scid mouse model of lymphatic filariasis may be important in investigation of the interaction of the murine, and possibly the human, immune system with the lymphatic filarial parasite.

Animals↗

PubMed1991

Insulin treatment prevents diabetes mellitus but not thyroiditis in RT6-depleted diabetes resistant BB/Wor rats.

Prophylactic insulin administration is known to prevent hyperglycaemia in diabetes prone BB rats and non-obese diabetic mice. This study investigated the effect of insulin treatment on the development of overt diabetes, clinically inapparent anti-islet autoreactivity, and thyroiditis in RT6-depleted diabetes resistant BB rats. Fewer than 1% of these animals develop spontaneous diabetes, but if depleted of RT6- T cells greater than 50% become hyperglycaemic. We treated 30-day-old diabetes resistant rats with anti-RT6.1 monoclonal antibody, exogenous insulin, or both. Up to 60 days of age, 16 of 20 rats given antibody alone became diabetic, compared with 1 of 20 also treated with antibody plus insulin. Up to 110 days of age, only 1 of 10 rats treated with both insulin and antibody between 30 and 60 days became diabetic. Histologic study of non-diabetic insulin plus anti-RT6 antibody treated rats revealed insulitis in 3 of 9 at 60 days old, and insulitis in 3 of 8 and thyroiditis in 6 of 7 at 110 days of age. Non-diabetic animals were also found to harbour autoreactive spleen cells that adoptively transferred diabetes. Splenocytes from 60 or 110-day-old non-diabetic donors that had been treated with insulin and antibody between 30 and 60 days of age induced diabetes in 7 of 13 and 6 of 8 adoptive recipients respectively. We conclude that insulin treatment prevents clinical diabetes in the RT6-depleted diabetes resistant BB rat, but this treatment does not prevent the development of autoreactive cell populations that cause thyroiditis and adoptively transfer diabetes.

Animals↗

PubMed1991

Reduction of the RT6.2+ subset of T lymphocytes in brown Norway rats with mercury-induced renal autoimmunity.

Chemically induced autoimmunity is a recently recognized environmental hazard that may affect individuals genetically predisposed to autoimmune disease and chronically exposed to certain chemicals. For example, moderate concentrations of mercury may lead to renal autoimmune disease in a small but significant percentage of the exposed population. Mercury also induces autoimmune glomerulonephritis in susceptible Brown Norway (BN) and MAXX inbred strain rats. Autoimmune responses, directed to epitopes of the renal glomerular basement membrane (GBM), are rapid in onset and have a self-limiting course in mercury-treated rats. Both regulatory T cells and idiotype-anti-idiotype network have been implicated in the resolution of this autoimmune process. In our investigations of immune regulation of mercury-induced autoimmune glomerulonephritis, we have used flow cytometry to quantitate lymphocyte subpopulations in the spleen and lymph nodes of mercury-treated and control BN rats. Of particular interest was the RT6+ T cell subset, that appears to have important immunoregulatory properties in a rat model of autoimmune insulin-dependent diabetes mellitus. Spleen and lymph nodes from control BN rats contained 22 and 52%, respectively, RT6+ cells. Spleens from mercury-treated animals contained 21% RT6+ cells on Day 10 of treatment, 13% on Day 17, 16% on Day 24 and 20% on Day 30. Lymph nodes from the same rats had 36% RT6+ cells on Day 10, 23% on Day 17, 29% on Day 24, and 28% on Day 30. The decrease in RT6+ cells correlated inversely with autoimmune responses to GBM, which peaked on Days 17-24 and declined by Day 30. Moreover, autoimmune responses were also associated with elevated RT6-:RT6+ T cell ratios. Similar results were obtained in two additional groups of BN rats, comprising both younger and older animals, sacrificed at Day 18 of mercury treatment. Analysis of other lymphocyte subpopulations demonstrated a decrease of CD4+ and CD5+ cells, whereas B cells as well as CD8+, IL-2 receptor+, and MHC class II+ subsets showed no consistent correlation with the onset or resolution of the autoimmune process. These findings suggest that mercury-induced changes in RT6+ T lymphocytes may be related to the development of renal autoimmune disease in genetically predisposed BN rats.

ADP Ribose Transferases↗