Infiltrating T cells from patients with primary Sjögren's syndrome express restricted or unrestricted T cell receptor V beta regions depending on the stage of the disease.

Organ-specific autoimmune diseases are usually considered to be mediated by autoreactive T cells which infiltrate the target tissue. Conceivably, these T cells could represent pathogenic autoreactive cells which recognize their specific antigen (peptide or superantigen) within the pathological tissue. Extensive studies dealing with the clonality of the infiltrating autoreactive cells gave conflicting results both in humans and animals. One possibility for explaining these contradictory data could rely on the stage of the disease when the T cell population is studied. Here, we report on this parameter by analyzing T cell receptor beta-chain variable regions of infiltrating T cells involved during one of the most frequent human organ-specific autoimmune disease, the primary Sjögren's syndrome. Six patients were selected on the basis of the duration of the disease before the biopsy procedure (two early and four late stages) to analyze initial and late T cell waves within the abnormal tissue. Using short-term interleukin-2-stimulated T cells, polymerase chain reactions, Southern and sequence analysis, we conclude that: (a) there is a clear restriction in the V beta usage by the infiltrating T cells only during the early stage of the disease, (b) this V beta restriction is related to a monoclonal T cell expansion, (c) the expanded V beta families are different from one patient to the other, and (d) there is no clear homology in length or amino acid composition in the CDR3 of the analyzed V beta regions. These results could provide an explanation to conflicting results on the V beta restriction usage during autoimmune diseases and could indicate time limitations in anti-V beta treatment. Furthermore, the monoclonal expansion of particular V beta-bearing T cells argues against a role for a superantigen during this disease.

Molecular analysis of T-cell receptor V beta chains of human T-cell chronic lymphocytic leukemia does not show intraclonal variability: implications for immunotherapy.

Human T-cell chronic lymphocytic leukemia (T-cell CLL) is a heterogeneous disease characterized by a monoclonal malignant proliferation of T cells in which the T-cell receptors (TCRs) can be, when expressed, considered to be membrane tumor-specific antigens. Owing to the increasing number of available monoclonal antihuman TCR reagents, it could be of interest to evaluate the feasibility of anti-TCR treatment during T-cell CLL. To test the therapeutic potentiality of anti-TCR monoclonal antibodies, we first analyzed the intraclonal variability in two terminally ill patients suffering from TCR alpha beta-positive cell CLL bearing different immunophenotypes. The cDNA corresponding to the variable regions of the TCR beta chains originating from the malignant T cells were amplified, cloned into M13 phages, and sequenced. The sequence analysis of multiple independent clones showed no intraclonal variability, with no evidence for ongoing hypermutation in the V beta region genes. The relevance of these findings with regard to an anti-V beta therapy and the comparison with similar analysis during B-cell monoclonal lymphoproliferations are discussed.