title: Spleen is a primary site for activation of platelet-reactive T and B cells in patients with immune thrombocytopenic purpura.
abstract: We have recently reported that in patients with chronic immune thrombocytopenic purpura (IMTP), circulating T and B cells that are responsive to gpIIb-IIIa can induce anti-platelet autoantibody production. In this study, the frequencies and activation status of gpIIb-IIIa-reactive T and B cells were evaluated in the peripheral blood and spleen obtained from nine IMTP patients undergoing splenectomy. There was no difference in gpIIb-IIIa-reactive T cell frequencies between peripheral blood and spleen (6.4 +/- 2.6 vs 5.2 +/- 2.4 per 10(5) T cells), as determined by limiting dilution analysis, but activated T cells responsive to gpIIb-IIIa showing accelerated proliferation kinetics and those expressing CD154 were more frequent in spleen than in peripheral blood. The frequencies of anti-gpIIb-IIIa Ab-producing B cells, as determined by ELISPOT assay, were also similar in peripheral blood and spleen (61.2 +/- 24.0 vs. 77.7 +/- 45.3 per 10(5) B cells); however, an anti-gpIIb-IIIa Ab was spontaneously produced by splenocytes in vitro, but scarcely secreted by PBMCs. CD19(-)/surface Ig(-)/CD38(+)/CD138(+) plasma cells secreting anti-gpIIb-IIIa Ab were exclusively detected in the spleen. In serial analysis, the frequencies of circulating gpIIb-IIIa-reactive T and B cells were markedly decreased after splenectomy in patients with a complete response, but were unchanged in nonresponders. These findings indicate that an interaction between gpIIb-IIIa-reactive T and B cells inducing anti-platelet Ab production in IMTP patients occurs primarily in the spleen and that the significant number of gpIIb-IIIa-reactive T and B cells activated in the spleen are released into the circulation as memory cells.
authors.affiliation: Institute for Advanced Medical Research and Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. kuwanam@sc.itc.keio.ac.jp
authors.forename: Masataka
authors.initials: M
authors.lastname: Kuwana
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Junichi
authors.initials: J
authors.lastname: Kaburaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000328:Adult; D000368:Aged; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001792:Blood Platelets / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D013156:Splenectomy; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D019039:Platelet Glycoprotein GPIIb-IIIa Complex