Anti-Sm autoantibodies in systemic lupus erythematosus mice: a model system for disease-specific autoreactivity

Eisenberg, Robert A.

doi:10.1007/bf00195290

Cited by 5 publications

(4 citation statements)

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“…chain cDNA of H6,GWK, As shown in Fig, 2, the T cell clone uses the Val4,2 element rearranged to a known Ja and the Ca element. The rearranged fi chain consists of the known elements Vy?14, Dy?2,l, J/?2,7 and DISCUSSION While antibody responses directed against snRNP are well analysed, both in human autoimmune disease [3,5,6,36] and animal models [ 18], T cell responses to this autoantigen have not yet been properly analysed. First evidence for the existence of snRNP-reactive T cells was provided by Cohen & Eisenberg by immunization of MRL mice [15,37], Two studies analysed proliferative responses of PBL from patients with connective tissue diseases using either purified natural snRNP-derived proteins [16] or recombinant UIsnRNP-specific 70-kD protein [17], However, in both cases proliferative responses were weak, and the nature and specificity of the responding cells were evaluated insufficiently.…”

Section: Cytokine Production By H6gwk Shows a Thi Patternmentioning

confidence: 99%

“…Some studies were performed in order to demonstrate the involvement of autoantigen-specific T cell responses in anti-snRNP autoantibody formation. Although polyclonal primary T cell responses to snRNP components were elevated with lymph node cells from Sm-immunized mice [15] and with peripheral blood mononuelear cells (PBL) from patients with SLE or MCTD [16,17], the specificity and function ofT cell responses remained unclear [18]. Since it is unsuitable to study T cell specificities by proliferative responses of bulk cell cultures.…”

Section: Introductionmentioning

confidence: 99%

“…Although polyclonal primary T cell responses to snRNP components were elevated with lymph node cells from Sm-immunized mice [15] and with peripheral blood mononuclear cells (PBL) from patients with SLE or MCTD [16,17], the specificity and function of T cell responses remained unclear [18]. Since it is unsuitable to study T cell specificities by proliferative responses of bulk cell cultures, 378 we started to address the problem of T cell function in antisnRNP autoimmunity anew by generating snRNP-reactive cloned T cell lines.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of an HLA-DR4-restricted T cell clone recognizing a protein moiety of small nuclear ribonucleoproteins (UsnRNP)

Wolff-Vorbeck

Hackl²,

Fenning³

et al. 1994

Clinical and Experimental Immunology

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SUMMARYIn sera of patients with mixed connective tissue disease (MCTD, Sharp Syndrome) high titres of IgG autoantibodies to UlsnRNP-specific proteins are found. The isolated occurrence of these autoantibodies is highly associated with the HLA-DR4 haplotype. snRNP-specific T cells are supposed to be involved in this autoantibody production. To address this question we cultured mononuclear cells from MCTD patients and healthy donors with a highly purified UsnRNP preparation from HeLa cells using bulk or limiting dilution cultures. Secondary responses to snRNP were detected only rarely with T cell lines from two patients and two controls, and turned out to be unstable during further expansion. One T cell line derived from a healthy individual retained its snRNP reactivity upon limiting dilution cloning and could be characterized in detail. The CD4+ T cell clone recognized native snRNP particles presented by monocytes in an HLA-DR4 (B1*0401)-restricted manner. Separation of the protein and RNA moieties of snRNP particles revealed that the T cell clone responded specifically to the protein fraction, but not to RNA and diverse control antigens. Sequencing of the T cell receptor a and ,B chain cDNAs revealed that the clone used the Val4.2 and VP 14 elements. Upon antigen-specific and mitogenic stimulation the T cell clone showed a Thl-specific cytokine pattern, and did not provide helper activity for in vitro immunoglobulin production. This study demonstrates the presence of self-reactive snRNP-specific T cells in a healthy donor. The T cell clone may not represent a helper T cell for the formation of UlsnRNP-specific autoantibodies.

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Section: Cytokine Production By H6gwk Shows a Thi Patternmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of an HLA-DR4-restricted T cell clone recognizing a protein moiety of small nuclear ribonucleoproteins (UsnRNP)

Wolff-Vorbeck

Hackl²,

Fenning³

et al. 1994

Clinical and Experimental Immunology

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“…The anti-Smith antigen test for lupus is a specific test used in dermatology. 34,35 Thus, a sensitive test with a negative result rules out disease (''SnOut'' mnemonic), whereas a specific test with a positive result rules in disease (''SpPin'' mnemonic). 36 Consequences of a false-positive test include inherent risks of potentially invasive follow-up testing, the social stigma associated with some diagnoses, anxiety and stress for the patient, and financial burden on the health care system.…”

Section: Diagnostic Testsmentioning

confidence: 98%