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Blood, 13 August 2009, Vol. 114, No. 7, pp. 1423-1428. Prepublished online as a Blood First Edition Paper on June 23, 2009; DOI 10.1182/blood-2009-01-200725. This Article Full Text Full Text (PDF) Supplemental Methods All Versions of this Article: blood-2009-01-200725v1 114/7/1423    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Ettinger, R. A. Articles by Pratt, K. P. PubMed PubMed Citation Articles by Ettinger, R. A. Articles by Pratt, K. P. Related Collections Immunobiology Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Lineages of human T-cell clones, including T helper 17/T helper 1 cells, isolated at different stages of anti–factor VIII immune responses Ruth A. Ettinger1,2, Eddie A. James2, William W. Kwok2,3, Arthur R. Thompson1,4, and Kathleen P. Pratt1,4 1 Puget Sound Blood Center, Seattle, WA; 2 Benaroya Research Institute, Seattle, WA; 3 Department of Immunology, University of Washington, Seattle; and 4 Department of Medicine, Division of Hematology, University of Washington, Seattle The development of neutralizing antibodies (inhibitors) after factor VIII (FVIII) infusions is a serious complication that affects approximately one-quarter of hemophilia A patients who have access to replacement therapy. To investigate the differentiation of naive T cells into FVIII-specific helper T cells that promote B-cell activation and antibody secretion, HLA-DRA-DRB1*0101-restricted T-cell clones that respond to a specific epitope in FVIII were isolated from a mild hemophilia A subject (the proband) 19 weeks and 21 months after his development of a high-titer inhibitor. Clones responding to the same epitope were also isolated from his multiply infused brother, who has not developed a clinically significant inhibitor. The 19-week proband clones were T helper (TH)17/TH1- or TH1/TH2-polarized, whereas all 8 clones isolated 21 months postinhibitor development were TH2-polarized cells. In contrast, all 6 clones from the brother who did not develop an inhibitor were TH1-polarized, indicating that tolerance to FVIII can be maintained even with circulating TH1-polarized cells that respond vigorously to in vitro FVIII stimulation. This is the first evidence that TH17/TH1-polarized cells play a role in hemophilic immune responses to FVIII. Furthermore, this is the first report of successful isolation and expansion of antigen-specific human TH17/TH1 clones using standard culture conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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