Spleen is a primary site for activation of platelet-reactive T and B cells in patients with immune thrombocytopenic purpura

Abstract

Spleen Is a Primary Site for Activation of Platelet-Reactive T and B Cells in Patients with Immune Thrombocytopenic Purpura1 Masataka Kuwana,2*† Yuka Okazaki,* Junichi Kaburaki,‡ Yutaka Kawakami,* and Yasuo Ikeda† 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 un- dergoing 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 105 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 105 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. The Journal of Immunology, 2002, 168: 3675–3682. C hronic immune (idiopathic) thrombocytopen

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