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

The BB rat is among the best models of insulin-dependent diabetes mellitus--with onset and pathogenesis closely resembling the human disease. One unusual feature is a severe T-cell lymphopenia, which appears to be inherited as a recessive trait controlled by a single gene, Lyp. Based on genetic analysis of several crosses, we show that development of diabetes involves at least three genes: Lyp, which is tightly linked to the neuropeptide Y (Npy) gene on chromosome 4, a gene linked to the major histocompatibility complex (MHC) on chromosome 20, and a third unmapped gene for which the Fischer rat strain carries an allele conferring resistance.
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PMID:Genetic dissection of autoimmune type I diabetes in the BB rat. 130 51

In a comparative study congenic rat strains bearing either the genetic background of diabetic BB/OK rats and the MHC (RTla) of diabetes-resistant LEW.1A rats (BB.1A/OK) or vice versa carrying the genetic background of LEW.1A rats in combination with the MHC (RTlu) of diabetic BB/OK rats (LEW.1BB/OK) and their parental rat strains BB/OK and LEW.1A were checked for insulin secretion of pancreatic islets, for the number of splenic and peripheral blood mononuclear cells (MNC) as well as for the mitogenic response of splenic MNC. Glucose stimulated insulin secretion of isolated islets of Langerhans was not different in 50, 70 and 100 day-old congenic rats and the progenitor rat strains excluding an impact of the genotype on this beta-cell-specific function. The number of splenic and peripheral blood MNC was reduced in BB/OK and BB.1A/OK rats compared to LEW.1A and LEW.1BB/OK rats. Splenic MNC from BB/OK and BB.1A/OK rats displayed a strongly decreased total [3H]thymidine incorporation under basal conditions as well as upon mitogenic stimulation by ConA in comparison with MNC from LEW.1A and LEW.1BB/OK rats. Thus, the occurrence of lymphopenia and the impairment of mononuclear cell proliferation in BB/OK rats is not related to the RTlu haplotype of the MHC but is linked to non-MHC genes as indicated by the phenotypic expression of these traits in congenic BB.1A/OK rats.
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PMID:Immunological and beta-cell-specific characteristics of diabetes-prone BB/OK rats and their congenic derivatives--a comparative study. 134 99

Tumor necrosis factor alpha (TNF-alpha), a major mediator of inflammation, also possesses a wide pleiotropism of actions, suggesting its involvement in physiological conditions. TNF-alpha mRNA is present in mouse embryonic tissues and also in fetal thymus and spleen. Repeated injections of a monospecific polyclonal rabbit anti-mouse TNF-alpha antibody in mice, starting either during pregnancy or at birth, led to a severe but transient growth retardation, already present at birth, reaching a 35% decrease in body weight at 3 wk, with complete recovery at 8 wk. The insulin growth factor I (IGF-I) blood levels were decreased to about 50%; growth hormone release and other endocrine functions were unaltered. A marked atrophy of the thymus, spleen, and lymph nodes was also observed, with lymphopenia and impaired development of T and B cell peripheral lymphoid structures. The pathways involving TNF-alpha in IGF-I release and early body growth are probably distinct from those by which TNF-alpha participates in early development of lymphoid tissues, where its low physiological release may contribute to enhance lymphoid cell expansion.
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PMID:Tumor necrosis factor alpha is involved in mouse growth and lymphoid tissue development. 140 71

Diabetes-prone BB rats spontaneously develop type 1 diabetes due to a T-cell-dependent destruction of insulin-producing beta-islet cells. A number of T-cell abnormalities including lymphopenia, poor cell-mediated responsiveness to alloantigen, and an absence of an RT6+ T-cell subset are associated with disease susceptibility. Our previous studies have implicated the thymic antigen-presenting cell in influencing disease potential and responsiveness to alloantigen. Since this cell type is also known to influence T-cell receptor expression in developing thymocytes, we examined the thymic and peripheral T-cell receptor beta chain variable region repertoire in diabetes-prone and diabetes-resistant rats. Our findings indicate that animals susceptible to diabetes induction have a characteristic and limited peripheral beta chain variable region repertoire that differs markedly from that expressed in the thymus.
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PMID:Identification of a limited T-cell receptor beta chain variable region repertoire associated with diabetes in the BB rat. 165 91

Spontaneously diabetic rats with remarkable polyuria, polyphagia, and polydipsia were discovered in 1983 in an outbred colony of Long-Evans rats purchased from Charles River Canada in 1982. They have since been maintained at the Tokushima Research Institute (Otsuka Pharmaceutical, Tokushima, Japan). A strain of rats (Long-Evans Tokushima Lean [LETL]) with diabetes was bred from these rats. The characteristic features of the disease in LETL rats are 1) sudden onset of polyuria, polyphagia, hyperglycemia, and weight loss; 2) no sex differences in the rate of onset or severity; 3) lymphocyte infiltration into islets followed by destruction of beta-cells and disappearance of lymphocytes at the onset of diabetes; 4) no significant T lymphopenia; 5) lymphocyte infiltration into the salivary glands and lacrimal glands; and 6) at least two recessive genes involved in the pathogenesis of insulitis, one of which is closely linked with RT1u. These characteristics closely resemble those of human insulin-dependent diabetes mellitus (IDDM). Results suggest that the LETL rat is a useful animal model for analysis of genetic and immunologic factors relating to the pathogenesis of human IDDM.
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PMID:New inbred strain of Long-Evans Tokushima lean rats with IDDM without lymphopenia. 168 94

Diabetes-prone (DP) BB rats spontaneously develop insulin-dependent diabetes resembling type 1 diabetes mellitus in man. They also exhibit lifelong T cell deficiency. The segregation of both diabetes and lymphopenia was studied in crosses between this inbred line of rats and the related but nondiabetic and nonlymphopenic inbred diabetes-resistant (DR) BB rat line. Diabetes segregated as a single, autosomal recessive trait and was always accompanied by lymphopenia. Among the limited number of differences in the genomic DNA sequences of the two lines, DP and DR BB, one may account for the development of diabetes and lymphopenia in the DP BB rats. It may be possible to screen the genomic DNA for such differences to detect a marker for the phenotypes.
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PMID:Diabetes segregates as a single locus in crosses between inbred BB rats prone or resistant to diabetes. 205 81

RT6 is an unusual cell membrane protein that is expressed exclusively by postthymic T cells. The inherent defect in its expression has been correlated to lymphopenia and genetically determined susceptibility for insulin-dependent diabetes mellitus in the rat. We report here the primary structure of the RT6.2 alloantigen as deduced from the cDNA sequence. The predicted amino acid sequence of RT6.2 begins with a conventional leader of 20 amino acids and ends in a hydrophobic C-terminal extension peptide of 29 amino acids as is common for phosphatidylinositol-anchored proteins. Native RT6.2 is predicted to comprise 226 amino acids, with a calculated Mr of 26,036. Four cysteine residues account for two intrachain disulfide bonds. The sequence lacks potential N-glycosylation sites and contains an excess of positively charged residues. Homology searches in protein sequence data banks suggest that RT6.2 is not encoded by a member of the immunoglobulin supergene family. Moreover, these analyses did not reveal any close homologies of RT6.2 to known proteins: the highest homology found was 21.2% identity in a 52-amino acid overlap to the torpedo acetylcholinesterase precursor. Southern blot analyses indicate that RT6.2 is the product of a single-copy gene and provide evidence for closely related genes in the mouse and other species. The corresponding gene products remain to be identified.
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PMID:Primary structure of rat RT6.2, a nonglycosylated phosphatidylinositol-linked surface marker of postthymic T cells. 230 May 88

BB/Wor diabetes-prone (DP) rats are lymphopenic and frequently develop insulin-dependent diabetes. Diabetes-resistant (DR) BB/Wor rats are not lymphopenic and become diabetic rarely and at a significantly younger age. To examine the genetic basis for diabetes, lymphopenia, and age at onset of diabetes among inbred BB/Wor rats, we crossed nonlymphopenic diabetic rats with lymphopenic DP animals and studied F1, F2, and backcross progeny. F1 rats were neither diabetic nor lymphopenic. Diabetes (both types) and lymphopenia reappeared among F2 rats, confirming the permissive association of diabetes and lymphopenia and the recessive nature of both. The absence of diabetes in F1 rats also suggested that the combination of genes responsible for diabetes among lymphopenic and nonlymphopenic rats may be distinct. Nonlymphopenic parental, F1, and F2 rats revealed normal lymphocyte subsets, including CD8+ and RT6+ T-lymphocytes. Lymphopenic parental and F2 rats revealed the absence of CD8+ and RT6+ cells, indicating that these T-lymphocyte abnormalities of lymphopenic DP rats segregate with the lymphopenia gene. The distribution of the ages at onset of diabetes among F2 lymphopenic and F2 intercross rats was significantly earlier than among lymphopenic parental and backcross animals, suggesting that the age of diabetes onset is a heritable trait and that the gene(s) or genetic modifier(s) responsible for the earlier onset of F2 diabetes was acquired from the nonlymphopenic parents. Our genetic studies also confirmed the observations that the 2- and 7-kilobase Bam HI fragments of the MHC class I region do not correlate with diabetes or lymphopenia.
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PMID:Genetic studies in inbred BB/Wor rats. Analysis of progeny produced by crossing lymphopenic diabetes-prone rats with nonlymphopenic diabetic rats. 256 83

Insulin-dependent diabetes is a chronic autoimmune disease probably mediated by T cells. We examined the alpha chain of the T-cell antigen receptor in two models of this illness (man and BB rat) to determine any association with autoimmune diabetes. We conducted a population study in man, using a human alpha chain probe, pGA-5, and restriction enzyme Bgl 11. Two allelic forms and three RFLP patterns, 2.8 and 3.0 kb homozygous and 2.8/3.0 heterozygous, were detected. There was no difference in the frequency of these RFLPs among the 50 Type I diabetic patients and 48 controls tested. BB rats develop a spontaneous T-cell mediated autoimmune diabetes. The diabetes has been linked in several breeding studies to an undetermined autosomal recessive gene causing T-cell lymphopenia. We were able to differentiate the T-cell antigen receptor alpha chain of the diabetic BB and control BBN rats using the restriction enzyme EcoR1 and a murine alpha chain probe, TT11. The BB rat had a haplotype characterized by the presence of 4.7 and 5.8 kb bands, and the absence of 1.4, 2.2, 2.6, 3.6, 3.9, 4.1, and 6.1 kb bands. In a breeding study with BB and BBN rats, diabetic animals of the F2 generation demonstrated no linkage with the BBs' alpha chain, nor was lymphopenia linked to the alpha chain of the BB rat. These results suggest that autoimmune diabetes is not linked to the T-cell antigen receptor alpha chain in the BB rat, nor is it associated with alpha chain constant region polymorphisms in Type I diabetes in man.
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PMID:T-cell antigen receptor alpha chain polymorphisms in insulin-dependent diabetes. 290 75

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


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