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

Lymphocytes from diabetes-prone Biobreeding rats consistently fail to generate T-cell-mediated cytotoxicity under conditions where cytotoxic T lymphocyte activity is readily demonstrated in normal rats. The failure is associated with generalized T-cell lymphopenia and marked reduction in the frequency of CD8+ cells. The few remaining CD8+ cells are widely held to be natural killer cells rather than class I major histocompatibility complex-restricted T lymphocytes. In this report we show that a detectable percentage of CD8+ lymphocytes express the T-cell receptor for antigen, thus identifying them as part of the T-cell lineage. The failure of these CD8+ T-cell-receptor-positive T cells to lyse target cells that are susceptible to T-cell mediated cytotoxicity is associated with markedly reduced expression of cell-surface CD8. Targets expressing higher than normal levels of class I major histocompatibility complex target antigen could be lysed, suggesting that reduction in CD8 has decreased T-cell activity for target antigen. We discuss the derivation of T cells that express low levels of CD8 and the role they could play in generating autoimmune diabetes.
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PMID:Cytotoxic T-cell precursors with low-level CD8 in the diabetes-prone Biobreeding rat: implications for generation of an autoimmune T-cell repertoire. 210 82

In summary, our bone marrow chimeras studies suggest that there are two defects in the BB rat associated with diabetes and/or lymphopenia, one residing at the level of the bone marrow lymphoid stem cell and the other within the T-cell differentiative environment, apparently postthymic. Our neonatal thymus transplantation studies and the adult thymus transplantation studies of others suggest a third defect in the BB rat, within the thymus itself, but this defect appears not to be responsible for the development of either the diabetes or the T lymphocytopenia. Rather, the thymic defect appears to control, at least in part, the lymphocyte hyporesponsiveness characteristic of the diabetes-prone BB rat. The role of the RT6 T-cell differentiation antigen in the etiopathogenesis of diabetes in this animal model remains unclear.
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PMID:The spontaneously diabetic BB rat: sites of the defects leading to autoimmunity and diabetes mellitus. A review. 219 61

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

Repeated large-volume blood withdrawals started at a young age previously appeared to correct lymphopenia and prevent diabetes in Ottawa diabetes-prone BB (BBdp) rats. Therefore, we sought an early effect 24 h after withdrawal of 25% of estimated blood volume and then reexamined the long-term effects in BBdp rats. The reexamination was prompted by the occurrence of variable numbers of BBdp rats positive for RT6.1 (a T-lymphocyte differentiation alloantigen) whose presence appears to "protect" against diabetes development (identified as BBp rats). Four groups were studied: non-diabetes-prone (BBn), RT6.1- BBdp, RT6.1+ BBp, and acutely diabetic BB (BBd) rats. An acute increase in the number of peripheral blood mononuclear cells and many subsets occurred in BBd and BBp rats. Despite these acute effects, a long-term effect of repeated blood withdrawal was not found in circulating cell counts or prevention of diabetes in BBdp rats. Thus, the previous finding was probably attributable to the presence of BBp rats. The long-term study demonstrated that RT6.1 expression in BBn rats increased from low levels at 15 days, peaked at 50 days, and decreased thereafter, an important finding in interpreting RT6.1 status at different ages. Furthermore, in contrast with other subsets, MARK-1+ B lymphocytes and OX42+ monocytes/macrophages decreased markedly in number at 120 and 150 days in BBn and BBp rats, whereas counts were higher and sustained in BBdp rats. The latter finding could be related to BBdp rats successfully resisting the autoaggressive process beyond the peak age of diabetes onset.
Diabetes 1990 Sep
PMID:Effects of single and repeated blood withdrawals on circulating mononuclear cells in BB rats. Failure to prevent diabetes despite acute changes in counts. 238 90

Diabetes prone BB (DP BB) rats are known to develop insulin dependent diabetes mellitus. In addition, a number of other immune abnormalities have been observed, like severe T lymphopenia, lack of CD8+ T cells, and lack of RT6+ T cells. Here we report double-labelling studies of lymph node T cells using MRC OX-32 (CD45R), and demonstrate that this T cell subset is absent in young adult DP BB rats. Since both RT6 and MRC OX-32 antigens are only expressed by mature peripheral T cells, it is tempting to speculate that the peripheral T cell pool of DP BB rats consists only of immature peripheral T cells, i.e. recent thymic emigrants.
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PMID:Peripheral T cells in diabetes prone (DP) BB rats are CD45R-negative. 253 58

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.
Diabetes 1989 Jul
PMID:Genetic studies in inbred BB/Wor rats. Analysis of progeny produced by crossing lymphopenic diabetes-prone rats with nonlymphopenic diabetic rats. 256 83

Previous studies have suggested that the development of diabetes in the BB rats does not require the expression of T lymphopenia. In order to derive non-lymphopenic diabetic rats and define the relationship between the T cell abnormalities, MHC genotype, and diabetes, we performed a cross between BB/H and diabetes resistant BB/control followed by an intercross of the F1. In the F2, the overall incidence of diabetes and lymphopenia was 30% and 27%, respectively. Lymphopenia was strongly associated with diabetes (p less than 0.001) and was seen in 76% of the diabetic F2's. However, 6 of the diabetic were non-lymphopenic (24%) and 3 of the non-diabetics were lymphopenic (5%). In the non-lymphopenic diabetic animals, all T cell levels were within the normal range, but diabetes occurred at an earlier age than their lymphopenic littermates (p less than 0.001). In contrast to the strong association between the inheritance of lymphopenia and diabetes, no relationship between diabetes and Class I MHC restriction fragment length polymorphisms was found. We conclude: 1) Diabetes and lymphopenia are strongly associated inherited abnormalities in the BB rat and are not associated with Class I RFLP defined genotypes within the RTIu haplotype, 2) Animals in whom diabetes occurs in the absence of lymphopenia can be derived using this breeding approach 3) In our non-lymphopenic rats, diabetes occurred at an earlier age possibly reflecting the restoration of quantitative or qualitative T cell defects found in lymphopenic BB rats.
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PMID:Derivation of non-lymphopenic BB rats with an intercross breeding. 257 92

In an outcross between a diabetic BB/H rat and a healthy Long Evans Hooded rat, the segregation of the RT6 gene was studied in the 207 F2 animals to look for linkage with diabetes or lymphopenia. The recessive gene, albino (c), was used as a marker for the RT6 gene because of the close proximity of these two genes on chromosome 1. Though most of the albino F2 rats should have been homozygous for the BB RT6 gene, we found no increase in the incidence of diabetes or lymphopenia among them when compared to their hooded littermates. Therefore, the RT6 gene was not linked to diabetes or lymphopenia in the BB rat. Moreover, the non-lymphopenic albino rats displayed normal RT6 expression when compared to the normal hooded rats showing that the RT6 gene from the BB/H grandfather was not defective. Any alteration in lymphocyte composition which could be specifically related to diabetes was studied by measuring all F2 rats for the major lymphocyte subsets including the RT6+ subset. We found that the typical pattern of lymphopenia described in diabetic BB rats was displayed by both diabetic and non-diabetic lymphopenic rats in the F2 generation. Thus, all these lymphocyte abnormalities including the depletion in RT6+ T lymphocytes appeared as a consequence of lymphopenia alone and could not be specifically related to diabetes.
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PMID:The gene for the T lymphocyte alloantigen, RT6, is not linked to either diabetes or lymphopenia and is not defective in the BB rat. 258 21

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

The spontaneously diabetic BB rat syndrome is associated with a marked lymphopenia, which affects all members of litters of diabetes-prone rats, and may be a necessary condition for the development of the disease. We assessed peripheral blood lymphocyte counts and subsets from birth to 66 days of age with a view to assessing the early time course. At birth, total numbers were decreased, as were total T-cells (monoclonal antibody W3/13+, with an even greater deficit in OX19+ cells), the helper/inducer subset (W3/25+), and the suppressor/cytotoxic subset (OX8+), but Ia+ (B, OX6+) cells were not reduced. There was a less-than-normal rise in these values with time, and a similar pattern was observed at 66 days. Rats followed thereafter to onset of diabetes showed no differences at 66 days that were predictive of subsequent diabetes development. Another set of rats studied at the same age and again at onset of diabetes showed no changes concurrent with diabetes onset. The data are consistent with a genetically determined defect in lymphocyte numbers that leads to a subnormal rise in circulating cells later in life, and may predispose to another unidentified factor responsible for precipitation of the beta cell cytotoxicity.
Diabetes 1985 Oct
PMID:Time course of the lymphopenia in BB rats. Relation to the onset of diabetes. 293 13


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