In situ expression of B7 and CD28 receptor families in skin lesions of patients with lupus erythematosus

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Abstract
Objective. To examine the expression of costimulatory molecules of the B7 and CD28 receptor families in active skin lesions of patients with systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE), and chronic discoid lupus erythematosus (CDLE). Methods. The in situ expression of B7-1, B7-2, BB-1, and CD28 was studied by immunohistochemistry, and B7-1 and B7-2 RNA expression was examined by reverse transcription-polymerase chain reaction. Results. Only in lesional skin from SLE, SCLE, and CDLE patients did dermal and epidermal antigenpresenting cells (APC) express B7-1 and B7-2, particularly when in apposition to CD28+ T cells. These B7-1 + and B7-2+ APC bound CTLA-4 fusion protein. In lesional (but not in nonlesional) skin, keratinocytes expressed BB-1. The majority of infiltrating T cells were CD28+. B7-1 and B7-2 RNA were expressed in lesional skin from SLE, SCLE, and CDLE patients; when dermis was separated from epidermis, only faint B7-1 and B7-2 RNA signals were detectable in the epidermis, indicating that dermal but not epidermal cells were the major source of B7-1 and B7-2 RNA. During treatment, both B7-1 and B7-2 protein and RNA expression were reduced. Conclusion. These in situ findings suggest that costimulation via the B7-CD28 pathway may be important for the generation and/or propagation of T cell activity in skin lesions of humans with lupus erythematosus. Thus, the manipulation of this pathway (e.g., by CTLA-4 fusion protein) could be an important target for the development of future therapies for LE.