Evidence for clonal expansion of T cell receptor V gamma II+ T cells in the synovial fluid of patients with arthritis.

We have demonstrated among synovial fluid T cells a unique profile of V gamma II sequences likely arising from clonally expanded T cells. We have determined the junctional diversity associated with each expressed V gamma family by resolving amplified fragments of cDNA into component parts on large denaturing gels. Among synovial fluid T cells we frequently find dominant fragments of a unique size clearly smaller than the dominant band observed with peripheral blood T lymphocytes. In some cases the dominant bands are 12 or 15 nucleotides smaller than the corresponding most abundant band from peripheral blood T lymphocytes. Patterns of lower m.w. species not typical of a polyclonal population argues that clones of T cells expressing the V gamma II family are expanding in the joint and that a high proportion of these cells do not express the V gamma IIJP sequence typical of peripheral blood but rather express V gamma II in combination with a shorter J fragment, JP1, JP2, J1, or J2. In addition by examining joint effusions from the left and right knees from the same individual we have shown that the profiles of V gamma II sequences derived from the fluids are identical to each other but clearly distinct from that of peripheral blood. We have, in addition, quantitated with a series of synthetic internal standards the relative usage of each V gamma family expressed by T cells in the synovial fluid and peripheral blood of seven patients with arthritis including six patients who were either children or adolescents and one adult patient. All patients showed a reduction in the relative expression of V gamma II in synovial T cells relative to peripheral blood T lymphocytes and a corresponding increase in the expression of V gamma I or V gamma III or both. We did not detect expression of V gamma IV in either lymphocyte population.