T Cell Receptor V¦Â Gene Expression In Systemic Lupus Erythematosus And P38mapk Activity

Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease of unknown cause that may affect the skin, joints, kidneys, lungs, nervous system, serous membranes, and other vital organs of the body. Patients with SLE develop distinct immunologic abnormalities, characterized by the production of autoantibodies. Accumulating evidence suggests that T cells are pivotal in the autoantibody response in B cells driven by autoantigens. T - cell receptor (TCR) is an important molecule that recognizes antigen in the form of short peptides bound to a major histocompatibility ( MHC) molecule. Functional TCR is generated by genetic rearrangement of the V, D, and J elements within the TCR gene cluster, accompanied by random addition of non - germline encoded N nucleotides, as well as pairing of different a and β chains. The major specificity of β T cells is based on the amino acid sequences encoded by the variable regions of the constituent TCR a and β chains. Evidence from animal models has shown that pathogenic T cells use a restricted set of T - cell receptor. Analysis of TCR V gene expression in autoimmune diseases is an area of intense interest because of implications regarding specific therapy. In addition, abnormalities in the signal transduction, induced either by antigen - receptor complex or systems of costimulatory cell - surface molecules, may result in immune cell dysfunctions in patients with SLEIn the present study, TCR Vβ1 - 20 gene subfamily expression and T cell clonality in patients with active SLE were analysed. Meanwhile, the levels of p38 MAPK in the peripheral blood lymphocytes (PBLs) from patients with SLE were detected.1. TCR Vβ1 - 20 gene subfamily expression in fifteen patients with active SLE was investigated semiquantitatively by RT - PCR and Southern blotting. The results showed that significant increases were found in Vβ8 and Vβ16 subfamily expression, when compared with healthy controls. The results indicate that there is preferential Vβ usage in lupus T cells when stimulated by autoantigens.2. Using RT - PCR and GeneScan, T cell clonality in PBLs from six patients with SLE was analysed. It was found that Vβ PCR products from two patients were derived from polyclonal T cells, however, Vβ9, Vβ2, Vβ1, Vβ2 PCR products from other four patients respectively were derived from oligoclonal T cells. The results suggest that the clonal expansions of lupus T cells may be driven by specific autoantigens.3. The levels of p38 MAPK in PBLs from fourteen patients with SLE were detected by immunoblotting. The total p38 MAPK (phosphorylation - state independent) levels in PBLs from patients with SLE were comparable to those from healthy controls, but the phosphorylated p38 MAPK (activated form) could not be detected. It was demonstrated that PBLs from patients with SLE have impaired p38 MAPK signaling.