Objective: To investigate whether T cell migration into different sites of inflammation (skin and synovium) within the same individual is principally regulated by tissue-specific homing or by more general mechanisms related to inflammation.
Methods: Expression of cutaneous lymphocyte antigen (CLA) and its ligand, E-selectin, was analyzed by immunohistochemistry and immunofluorescence using paired skin and synovial membrane (SM) samples from patients with psoriatic arthritis (PsA). To investigate disease specificity, delayed-type hypersensitivity (DTH) skin lesions, induced by tuberculin purified protein derivative, and SM from patients with rheumatoid arthritis (RA), were studied as controls. To directly examine cell migration in in vivo, the proportion of CLA+ T lymphocytes migrating into suction-induced skin blisters was assessed by flow cytometry. Using the same technique, levels of paired peripheral blood and synovial fluid (SF) T cells were also analyzed.
Results: CLA+ T cells preferentially accumulated in the skin, but not in the joint, of patients with PsA. Similarly, CLA+ T lymphocytes predominated in the DTH skin lesions of RA patients, but were very rare in the SM of RA patients, and were scarcely represented in the SF of patients with several chronic inflammatory arthropathies. In addition, CLA+ T lymphocytes preferentially migrated into epidermal skin blisters. This preferential pattern of CLA+ T cell accumulation was not related to the selective expression of E-selectin, since this was similar in the skin and SM of both PsA and RA patients.
Conclusion: The distinct pattern of T cell infiltration into sites of inflammation within the skin and synovium is regulated by both organ-specific homing and general inflammation-related mechanisms.