T cell receptor beta chain gene rearrangement shared by murine T cell lines derived from a site of autoimmune inflammation.

Abstract

Advances in our understanding of the structure and molecular biology of the T lymphocyte antigen-receptor have now made it feasible to study human autoimmune diseases using new approaches. One such approach involves cloning of T cells from sites of autoimmune pathology followed by identification of putative disease-related T cell oligoclonality at the level of the T cell receptor gene rearrangements. We have now tested the feasibility of this approach in an animal model of autoimmunity, murine experimental allergic encephalomyelitis (EAE). Spinal cord-derived, self (murine) myelin basic protein (MBP)-reactive T cell lines and sublines were analyzed at the level of their receptor beta chain rearrangements using Southern blots. We now report that the MBP-reactive T cell lines and sublines derived from the spinal cords of four of five SJL/J mice with EAE share a 14.5-kb rearranged T cell receptor beta 1 band on Southern blots. A spinal cord-derived T cell line that was reactive to purified protein derivative of tuberculin (PPD), several lymph node-derived ovalbumin-and PPD-reactive T cell lines, as well as one MBP-reactive spinal cord-derived T cell line did not share this 14.5-kb rearranged beta 1 band. These results suggest that analysis of the antigen receptors used by T cells cloned from sites of inflammation may be a useful initial approach for identifying pathogenetically relevant T cells in the study of certain human autoimmune diseases.

Clonal heterogeneity of synovial fluid T lymphocytes from patients with rheumatoid arthritis.

“…The adjuvant arthritis model is of additional interest because in vitro attenuation of arthritogenic cloned T cells endows such lymphocytes with the capacity to vaccinate against the disease, possibly by activating anti-idiotypic immune responses against the antigen receptor on the attenuated cloned T cells (14,17,25). Similar observations have been made in experimental allergic encephalomyelitis, an animal model of multiple sclerosis (30)(31)(32)(33)(34). If a clonally restricted T-cell response to an identifiable antigen were of similar importance in human RA, our understanding of this disease would be dramatically improved.…”

Chronic Sclerosing Sialadenitis of the Submandibular Gland is Mainly Due to a T Lymphocyte Immune Reaction

“…This may explain the different stages in chronic sclerosing sialadenitis. Observations in experimental allergic encephalomyelitis in mice suggest that the lymphocytes in damaged tissue express only a limited number of variable T-cell receptor gene regions and react with a single or a few epitopes, as observed in organspecific autoimmune diseases (21)(22)(23). In autoimmune diseases such as multiple sclerosis or rheumatoid arthritis, a pronounced clonal expansion of ␥␦ T lymphocytes has been observed (17,18).…”

Differential utilization of regulatory domains within the alpha 1(I) collagen promoter in osseous and fibroblastic cells.

“…Genomic DNA was prepared from stably transfected cell populations or tissues from transgenic animals as described previously (Padula et al ., 1988) . DNA was restricted with EcoRI or Pvull, separated on a 1% agarose gel, transferred to a nylon membrane (Zetabind ; Cund Inc ., Meriden, CT), and hybridized as described (Singh and Jones, 1984), except for the following modifications : the transfer was done by capillary blotting and the hybridization contained as additional components 10% dextran sulfate, 30% formamide, 0.1% Sarkosyl instead of sodium dodecyl sulfate, and 0.1 mg/ml salmon sperm DNA .…”