Human normal non hematopoietic cells of mesenchymal and neuroectodermal origin may express functional IL-Rs. For instance, in these cell types, IL-2 can stimulate proliferation (endothelial, intestinal and nervous cells) or modify the expression of adhesion molecules (fibroblasts) or inhibit proliferation (bone marrow stromal cells). Therefore, some cytotoxic effects described during IL-2 biotherapy could be due to a direct interaction between IL-2 and non-hematopoietic tissues. The expression of functional IL-2-R has also been reported in several human cell lines derived from solid tumors. In some instances IL-2 inhibits cell growth (head and neck, gastric and renal carcinomas), but in other tumors, growth stimulation and increased expression of markers of tumor progression have been reported (intestinal, breast, and lung carcinomas, gliomas, fibrosarcomas and melanomas). Additionally, secretion of biologically active IL-2 has been reported in some melanoma and breast cancer cell lines. Transcripts for the novel cytokine IL-15, which utilizes the beta and gamma chains of the IL2-R, have been found in melanoma cells and anti-IL-15 mAbs inhibit HLA class I expression in these cells. Therefore these cytokines may modify, inside a tumor, the behavior of both stromal and neoplastic cells. All these data may have important implications in our understanding of tumor host interactions and in future strategies of immunotherapy.

Endothelium, Vascular↗

PubMedDate not supplied

dsDNA-, nucleohistone- and DNASE I-reactive T lymphocytes in patients affected by systemic lupus erythematosus: correlation with clinical disease activity.

OBJECTIVE: To demonstrate the involvement of T lymphocytes reactive to autoantigens in the pathogenesis of autoimmune diseases and to analyse their clinical relevance. METHODS: The frequency of T cell clones reactive to double strand DNA (dsDNA), Nucleohistone (NH) complex and Dnase I was calculated for the peripheral blood mononuclear cells (PBMC) of 15 SLE patients and 9 healthy subjects by proliferation assay. RESULTS: DsDNA- and NH-specific T cell clones were found in the majority of the patients analysed (frequency ranging from 2 to 50 clones/10(7) PBMC), while their absence or very low frequency (2 clones/10(7) PBMC) was observed in the control PBMC. Their frequency significantly correlated with decreased serum concentrations of C3 and C4 and with the systemic lupus erythematosus disease activity index (P = 0.03). A very low frequency of Dnase I-reactive T cell clones was observed in both SLE and healthy subjects. CONCLUSION: Our results suggest that dsDNA- and NH-reactive T lymphocytes may be involved in the pathogenesis of SLE and that their quantification in the peripheral blood of patients could be a useful tool to follow the clinical course of the disease.

Adult↗

PubMedDate not supplied

Anti-CD4 monoclonal antibody (mAb) and anti-idiotypic mAb to anti-CD4 in the therapy of autoimmune diseases.

The present report critically reviews the rationale, experimental and clinical effectiveness and limits of anti-CD4 monoclonal antibody (mAb) therapy. References are also made to a novel approach involving active immunotherapy and an anti-idiotypic mAb bearing the internal image of human CD4 antigen. Preliminary observations concerning the effects of this treatment in one patient with rheumatoid arthritis and in one patient with systemic lupus erythematosus are reported.

Antibodies, Anti-Idiotypic↗