To document the in vivo interactions occurring between the immune system and HIV replicating cells, we analyzed using in situ hybridization the production of IL-1#, and INF-y in eight hyperplastic lymph nodes from HIV-1 infected patients. Numerous IL-1ft-and IL-6-producing cells associated in clusters were detected in sinuses. Few individual IL-1l#-and IL-6-producing cells were present in interfollicular and follicular areas. IL-2-and INF-'y-producing cells were observed in all lymph node compartments, with a selective enrichment in germinal centers. The amount and distribution of
Myasthenia gravis (MG) is an autoimmune disease targeting the skeletal muscle acetylcholine receptor. We have previously demonstrated a selection bias of CD4+ T cells expressing the Vβ5.1 T‐cell receptor gene in the thymus of HLA‐DR3 patients with MG. To evaluate the pathogenicity of these cells, severe combined immunodeficiency mice engrafted with MG thymic lymphocytes were treated with anti‐Vβ5.1 antibody. Signs of pathogenicity (eg, acetylcholine receptor loss and complement deposits at the muscle end plates of chimeric mice) were prevented in anti‐Vβ5.1–treated severe combined immunodeficiency chimeras. Pathogenicity was mediated by autoantibodies against acetylcholine receptor. Thymic cells depleted of Vβ5.1‐positive cells in vitro before cell transfer were nonpathogenic, indicating that Vβ5.1‐positive cells are involved in the production of pathogenic autoantibodies. Acetylcholine receptor loss was prevented by Vβ5.1 targeting in HLA‐DR3 patients only, demonstrating specificity for HLA‐DR3–peptide complexes. The action of the anti‐Vβ5.1 antibody involved both the in vivo depletion of Vβ5.1‐expressing cells and an increase in the interferon‐γ/interleukin‐4 ratio, pointing to an immune deviation–based mechanism. This demonstration that a selective and specific T‐helper cell population is involved in controlling pathogenic autoantibodies in MG holds promise for the treatment of MG.
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