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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Initial reports of blood T cell subsets in insulin-dependent (type I) diabetes mellitus (IDDM) are conflicting and, consequently, difficult to relate to animal models of the disease. To minimize technical artefacts, which may have contributed to previous results, we used direct immunofluorescence on whole blood and counted 3,000 lymphocytes by flow cytometer. Forty-two IDDM patients divided in three groups of 14 according to the disease duration and 12 age and sex matched controls were studied for T3, T4, T8 and HLA-DR expression. No statistically significant differences were found in their total blood lymphocyte counts or in the percentage of T3, T4 and T8 positive cells, although mild lymphopenia was found in the group of long-standing diabetics. The percentage of activated T cells, identified as T3+/DR+ cells, was significantly increased in the groups of patients studied more than a month after diagnosis and in four of 14 patients studied within a month from diagnosis. Seven new onset IDDM patients were studied for co-expression of T8 and Leu 15 antigens (putative suppressor cell phenotype), but no significant differences was found compared with controls. We conclude that T4/T8 ratio abnormalities previously reported in Ficoll separated cells are not reproduced when unseparated cells are analysed by flow cytometry, although the presence of HLA-DR+ T cells is confirmed.
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PMID:T-lymphocyte subpopulations in insulin-dependent (type I) diabetes mellitus. 293 83

Injection of major histocompatibility complex (MHC)-compatible bone marrow cells from normal animals into neonatal BB rats resulted in a striking decrease in incidence of diabetes and restoration of concanavalin A (ConA) and mixed lymphocyte responses. However, injection of bone marrow cells pretreated with anti-rat thymocyte antiserum plus complement to remove mature T cells had no effect on incidence of disease, suggesting that mature T cells in the bone marrow inoculum were responsible for prevention of diabetes. Because the decreased incidence of diabetes in rats injected with untreated bone marrow appeared to be unrelated to the extent of lymphopenia in these animals, the involvement of T cells in the onset of diabetes must reflect a defect in the normal function of these cells rather than their absolute number. Approximately 50% of the W3/13+ cells in the spleens of BB rats lacked the OX-8 and W3/25 T cell subset markers. The identity of this W3/13+, OX-8-, W3/25- blank subset remains to be established. Our results, interpreted in light of studies from the other laboratories, suggest the existence of multiple abnormalities in the BB rat, including the presence of T cells as effector or helper cells that augment onset of disease and the absence of a regulatory T cell circuit that could prevent the disease.
Diabetes 1986 Sep
PMID:Prevention of diabetes in BB rats. I. Evidence suggesting a requirement for mature T cells in bone marrow inoculum of neonatally injected rats. 294 18

The BB rat diabetic syndrome has been prevented by various immunosuppressive and reconstitution measures. We observed an effect of multiple blood samplings on diabetes incidence and examined its immunological correlates. Individual litters were divided into two groups; one was sampled and the other was sham sampled as the control group. Sixty-four diabetes-prone and 59 non-diabetes-prone rats were studied. The sampled rats had blood removed at 15 (28% of total blood volume), 30 (30%), 50 (21%), 75 (16%), and 120 days of age. The sham-sampled control rats had blood removed only at 120 days of age. The incidence of diabetes in the sampled group was markedly lower than that of their sham-sampled littermates (22 vs. 78%). This result was associated with a correction of their OX19+ (pan-T-lymphocytes) and W3/25+ (helper/inducer) T-lymphocyte-number defects. An increase in lymphocyte subsets was also seen in the non-diabetes-prone BB rats, significant for all but the OX19+ cells. Islet pathology and pancreatic insulin content were consistent with metabolic outcomes. The effect of blood withdrawal thus has implications for understanding the pathogenesis of both the diabetes syndrome and the lymphopenia of the BB rat. Furthermore, it suggests that a stimulation of lymphopoiesis by blood withdrawal (analogous to that of erythropoiesis) may be a hitherto unrecognized physiological response in normal animals.
Diabetes 1988 Mar
PMID:Diabetes prevention in BB rats by frequent blood withdrawal started at a young age. 296 14

We randomly assigned 46 patients (mean age, 11.7 years; range, 4.5 to 32.8) with newly diagnosed insulin-dependent diabetes mellitus within two weeks of beginning insulin to receive either corticosteroids for 10 weeks plus daily azathioprine for one year or no immunosuppressive therapy. Half the 20 immunosuppressed patients completing the one-year trial had satisfactory metabolic outcomes (hemoglobin A1c less than 6.8 percent; stimulated peak C peptide greater than 0.5 nmol per liter; insulin dose less than 0.4 U per kilogram of body weight per day) as compared with only 15 percent of the controls. Three of 20 immunosuppressed patients, but no controls, were insulin independent at one year. Two of these continue to receive azathioprine without insulin after more than 27 months of follow-up. The response to immunosuppression correlated with older age, better initial metabolic status, and lymphopenia (less than 1800 lymphocytes per cubic millimeter) resulting from immunosuppression. The side effects of azathioprine included vomiting in one patient and mild hair loss in several others. Prednisone use resulted in a transient cushingoid appearance, weight gain, and hyperglycemia. The growth rate remained normal in all patients. We conclude that early immunosuppression with short-term use of corticosteroids plus daily azathioprine can improve metabolic control in some patients with insulin-dependent diabetes mellitus, but results from this unblinded study are preliminary and require further confirmation and long-term follow-up.
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PMID:Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus. 304 45

The effects of cyclosporin A (Cs-A) and insulin on peripheral lymphocytes in BB/W rats were studied. The cumulative incidence of overt diabetes in untreated BB/W rats was 72% up to 120 days of observation, whereas the incidence was 13% in Cs-A-treated rats. Lymphocytopenia, consisting of decreased OX19+ (pan T), W3/25+ (helper/inducer T) and OX8+ (cytotoxic/suppressor T) cells, was present in BB/W rats. Cs-A significantly decreased both the percentage and the absolute number of OX8+, OX6+ (Ia-positive) and OX12+ (B) cells, and augmented the ratio of W3/25+ to OX8+ cells in BB/W rats. On the other hand, insulin injection significantly decreased the percentage of OX6+ cells and the ratio of W3/25+ to OX8+ cells in BB/W rats. Thus, rearrangement of the ratio of helper/inducer T to cytotoxic/suppressor T cells and reduction in the number of Ia antigen-bearing cells could be important for the inhibitory effects of diabetes in BB/W rats upon treatment with Cs-A or insulin.
Diabetes Res 1988 Jul
PMID:Effects of cyclosporin A and insulin on peripheral lymphocytes in BB/W rats. 306 53

Diabetes-prone Bio-breeding/Worcester (DP) rats exhibit a severe T cell lymphopenia and autoimmune pancreatic insulitis. The present results indicate that the T cell lymphopenia is due in large part, if not entirely, to the absence of the RT-6+ peripheral T cell subset, which includes members of both the helper/inducer (W3/25) and suppressor/cytotoxic (OX 8) antigenic phenotypes. Delineation of the causal mechanism(s) for the selective absence of RT-6+ T cells in DP rats may provide important insights into the cellular basis of the insulin-dependent diabetes mellitus syndrome in these animals.
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PMID:Absence of the RT-6 T cell subset in diabetes-prone BB/W rats. 307 5

Rats of the BB strain develop diabetes mellitus in a high percentage and display a severe T-cell lymphopenia. In order to investigate the role of micro-environmental factors in the T-cell maturation in BB rats the postnatal development of macrophage subpopulations and T-lymphocyte subsets, in addition to the specific immune response in situ, were studied in thymus, spleen and lymph nodes of BB rats. Wistar rats were used as controls. From the day of birth on, a severe reduction was noticed in the macrophage subpopulations in the thymic cortex of BB rats, but not in spleen and lymph nodes, as compared to Wistar rats. The population of T-suppressor/cytotoxic cells (OX8-positive cells) did not increase any longer from Day 10 after birth in the thymic cortex and from Day 14 in spleen and lymph nodes. This is indicative for an intrathymic maturational defect of the OX8-positive cells in BB rats. No deviations could be observed in the development of the T-helper (ER2-positive) cell population. Young adult BB rats were as capable as Wistars of developing a specific immune response to thymus-independent (TI) antigens, but the response to a thymus-dependent (TD) antigen was delayed and decreased. Also the distribution pattern of the specific antibody-containing cells in a TD response in BB rats differed from that in Wistar rats. The ER2-positive cells, although present in normal numbers, may function insufficiently as T-helper cells in BB rats.
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PMID:Neonatal development of lymphoid organs and specific immune responses in situ in diabetes-prone BB rats. 326 12

Spontaneous diabetes was fully prevented in 65 BB/hooded (BB/h) highly diabetes-prone hybrid rats that were given five intraperitoneal injections (25 to 30 x 10(6) cells/injection) of fresh splenocytes or concanavalin A (ConA)-activated cultured splenocytes (blasts) from the diabetes-free Wistar-Furth or Long-Evans strains during the first 2 postnatal wk. Rats remained under observation for up to the age of 180-200 days. Of 70 littermate controls that received no cell injections, 63 developed overt diabetes before the age of 180 days. One intraperitoneal injection (25 x 10(6) cells) of splenocytes or blasts given during the first 36 h after birth was not as effective as multiple injections in preventing overt diabetes. Mild insulitis was present in 4 of 59 "protected" rats; small, discrete mononuclear infiltrates in periductular connective tissue and/or between pancreatic acini were observed in 27. Nondiabetic BB/h rats that were protected with splenocytes or blasts from diabetes-free strains had the same degree of lymphopenia in peripheral blood and spleen as age-matched, insulin-treated diabetic BB/h rats, but the level of islet cell surface antibodies in their serum was significantly lower. The same neonatal injections that protected rats from the development of spontaneous diabetes were completely ineffective in preventing the adoptive transfer of diabetes later in life by the injection of blasts from acutely diabetic BB/h rats.
Diabetes 1988 Aug
PMID:Prevention of spontaneous but not of adoptively transferred diabetes by injection of neonatal BB/hooded hybrid rats with splenocytes or concanavalin A blasts from diabetes-free strains. 339 42

The BB/Wor rat is an animal model of spontaneous autoimmune type I diabetes mellitus. Previous reports have emphasized the presence of lymphopenia in all diabetic and diabetes-prone BB rats. This manuscript reports the appearance of diabetes among three family lines of BB/Wor animals that were previously free of diabetes. Diabetic W-line rats are not lymphopenic and possess normal percentages of phenotypic T cell subsets. Hence the presence of lymphopenia is not obligatory for the occurrence of diabetes in BB/Wor rats.
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PMID:Diabetic BioBreeding/Worcester (BB/Wor) rats need not be lymphopenic. 348 83

Several immunological responses of the spontaneously diabetic BB rat colony in Edinburgh designated (BB/E) have been studied. The proliferative responses to Con A and LPS, ability to make IL-2 and to show NK activity have been studied using diabetic and non-diabetic BB/E rats and normal Wistar rats. Our data suggest that the diabetic animals in the BB/E colony do not have marked deficiencies in any of these parameters. Lymphopenia and depressed T-cell responses do not appear to be a prerequisite for the development of diabetes in the BB/E colony.
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PMID:Immunological responses of the BB rat colony in Edinburgh. 349 4


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