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ABSTRACT: Rotavirus infections have been implicated as a possible trigger of type 1 diabetes. We elucidated this connection by comparing peripheral blood T cell responses to rotavirus between children with newly diagnosed type 1 diabetes (n = 43), healthy children with multiple diabetes-associated autoantibodies (n = 36) and control children carrying human leukocyte antigen (HLA)-conferred susceptibility to type 1 diabetes but without autoantibodies (n = 104). Lymphocyte proliferation assays based on stimulation with an antigen were performed using freshly isolated peripheral blood mononuclear cells (PBMC) and IgG and IgA class rotavirus antibodies were measured using plasma samples collected from the children. The expression of interferon (IFN)-gamma, interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-beta in PBMC was studied with real-time polymerase chain reaction (PCR) in a subgroup of 38 children. No differences were observed in the strength or frequency of positive T cell responses to rotavirus between children with overt diabetes, children with multiple autoantibodies and control children. Children with diabetes-associated autoantibodies had, instead, stronger T cell responses to purified coxsackie B4 virus than control children. Rotavirus-stimulated lymphocytes from autoantibody-positive children produced more IL-4 and phytohaemagglutinin (PHA)-stimulated lymphocytes more IL-4 and IFN-gamma than lymphocytes from control children. PHA-stimulated lymphocytes from children with diabetes also produced more IL-4 and purified protein derivative (PPD)-stimulated lymphocytes less TGF-beta than lymphocytes from autoantibody-negative control children. In conclusion, our lymphocyte proliferation studies did not provide evidence supporting an association between rotavirus infections and the development of type 1 diabetes or diabetes-associated autoantibodies in young children.
Clinical & Experimental Immunology 09/2006; 145(2):261-70. · 3.36 Impact Factor
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ABSTRACT: Rotavirus is a major cause of gastroenteritis in young children. Antibodies seem to protect against rotavirus infection but cell-mediated immune responses are probably also important for protection. We evaluated the development of T-cell responses to rotavirus in follow-up samples from 20 healthy children with an increased genetic risk for type 1 diabetes. Blood samples from 16 healthy adults were also available for the study. T-cell proliferation was analysed at 3-6 month intervals from the age of 3 months to the age of 4-5 years using the Wa strain of human rotavirus and the NCDV strain of bovine rotavirus as antigens. IgG and IgA antibodies to rotavirus were studied from simultaneously drawn plasma samples with EIA method using NCDV as an antigen. A total of 24 infections were revealed by antibody analysis. Sixteen children showed diagnostic increases in both IgG and IgA antibodies to rotavirus, while 5 children showed increases in IgA antibodies only and 3 in IgG only. Antibody rises were accompanied by T-cell responses to rotavirus (SI > 3) in 9 of the 24 cases. T-cell responses to purified or lysed human rotavirus were stronger after a rise in rotavirus antibodies than the responses before infection (P = 0.017 and 0.027, respectively). There was a correlation between T-cell responses to purified and lysed human rotavirus and NCDV. Strong T-cell responses to rotavirus were transient and the ability to respond usually disappeared in one year, but in all adults T-cell responses to rotavirus were strong implicating that several infections are needed to develop consistent, strong T-cell responsiveness.
Clinical & Experimental Immunology 07/2004; 137(1):173-8. · 3.36 Impact Factor
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ABSTRACT: Measles virus (MV)-induced immune suppression is an important reason for MV-associated mortality and morbidity. Despite numerous studies, the mechanisms of immune suppression still remain poorly defined. In the present study we analyzed the effect of MV components on the T-cell recognition of specific non-MV antigens. We demonstrated that even inactivated MV could inhibit the presentation of unprocessed protein antigen to specific T cells, whereas MV did not affect the responses of specific T cells to representative synthetic peptide epitopes derived from complex antigens. The inhibition was induced by MV-infected cell membranes. The kinetics of the MV-dependent inhibition suggested an impaired antigen processing in mononuclear cells as addition of MV-infected cell debris 4 h after the beginning of cell cultures no longer inhibited T-cell responsiveness.
Virology 02/2001; 279(2):422-8. · 3.35 Impact Factor
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ABSTRACT: T cell epitopes of the measles virus (MV) nucleoprotein were studied by synthesizing overlapping 20 aa peptides over the known sequence of the protein and analysing the proliferation responses of a panel of MV-specific T cell lines and clones against these peptides. T cell lines were established from eleven healthy controls and seven multiple sclerosis patients, all with a history of past MV infection. The epitopes recognized by these lines were concentrated in a few regions of the polypeptide chain. Overlapping peptides containing aa 321-340 and 331-350 were most often recognized. Other epitopes were detected close to the amino-terminal end of the polypeptide chain as each of the peptides 1-20, 21-40, 31-50 and 51-70 contained stimulating moieties. Some responses were also detected towards peptides 151-200 and 221-250, but the carboxy-terminal end of the polypeptide was not recognized by any of the tested T cell lines. The amino acid sequences of the peptides that stimulated the T cell clones and lines, as a rule, contained binding motifs described for HLA-DR alleles found in T cell donors. The regions of protein sequence which did not reveal any T cell epitopes were, instead, relatively free of binding motifs. The results suggest that only a few epitopes of the MV nucleoprotein are important in establishing T cell immunity.
Journal of General Virology 08/1999; 80 ( Pt 7):1609-15. · 3.36 Impact Factor
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ABSTRACT: To characterize T cell-recognized epitopes on rubella virus (RV) E1 glycoprotein, IL-2-dependent RV-specific T cell lines were established from 14 rubella-seropositive healthy donors. The responses of these lines were studied by using a panel of 94 partially overlapping synthetic peptides of 15 amino acids (aa) length covering the known nucleotide sequence of RVE1 glycoprotein. Two to seven peptide-defined epitopes were recognized by the T cell lines, but a large interindividual variation was found. T cell reactivity was most often localized to the regions between aa 276 and 290, aa 381 and 395 and aa 410 and 420. Analysis of overlapping, truncated peptides revealed three minimal T helper cell epitopes VIGSQARK, KFVTAALLN and RVIDPAAQ in aa positions 280-287, 385-393 and 412-419, respectively.
Clinical & Experimental Immunology 07/1996; 104(3):394-7. · 3.36 Impact Factor
