Analysis of human T cell and B cell responses against U small nuclear ribonucleoprotein 70-kd, B, and D polypeptides among patients with systemic lupus erythematosus and mixed connective tissue disease.
OBJECTIVE
To analyze T and B cell reactivity with U small nuclear RNP (snRNP) 70-kd, B, and D polypeptides among patients with connective tissue disease (CTD) and to examine the functional characteristics of snRNP-reactive T cell clones.


METHODS
We used an snRNP enzyme-linked immunosorbent assay and immunoblotting to characterize antibodies in patients' sera. We used human recombinant fusion proteins 70 kd, B, and D to stimulate and clone snRNP-reactive T cells from CTD patients. We analyzed the cell surface phenotype, antigenic specificity, and cytokine profiles of T cell clones.


RESULTS
Patients showed T cell responsiveness to snRNP polypeptides that paralleled their autoantibody reactivities. A total of 256 clones were generated, and clones were identified which were specific for the 70-kd, B, or D polypeptides. Clones expressed a T helper cell phenotype, and were found to produce substantial quantities of both interleukin-4 (IL-4) and interferon-gamma, and lesser quantities of IL-2 and IL-6.


CONCLUSIONS
These results show that CTD patients have clonable circulating snRNP-reactive T cells that parallel the specificity of snRNP-reactive antibodies in their sera. The snRNP-reactive T cells exhibit a helper cell phenotype and produce cytokines which are important in B cell help and differentiation.
Holyst
M M
MM
University of Missouri-Columbia and Harry S Truman Memorial Veterans Hospital, USA.
Hill
D L
DL
Hoch
S O
SO
Hoffman
R W
RW
D000328:Adult; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D001323:Autoantibodies; D016207:Cytokines; D010455:Peptides; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D017411:Ribonucleoproteins, Small Nuclear