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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3439-3446. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2002-12-3936. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3936v1 102/9/3439    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jung, U. Articles by Fowler, D. H. Search for Related Content PubMed PubMed Citation Articles by Jung, U. Articles by Fowler, D. H. Related Collections Immunobiology Neoplasia Transplantation Signal Transduction Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION CD3/CD28-costimulated T1 and T2 subsets: differential in vivo allosensitization generates distinct GVT and GVHD effects Unsu Jung, Jason E. Foley, Andreas A. Erdmann, Michael A. Eckhaus, and Daniel H. Fowler From the Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and the Office of Research Services, Veterinary Resources Program, National Institutes of Health, Bethesda, MD. Adoptive T-cell therapy using CD3/CD28 co-stimulation likely requires in vivo generation of antigen specificity. Because CD28 promotes TH1/TC1 (T1) or TH2/TC2 (T2) differentiation, costimulation may generate donor T1 or T2 cells capable of differentially mediating allogeneic graft-versus-tumor (GVT) effects and graft-versus-host disease (GVHD). Costimulation under T1 or T2 conditions indeed generated murine TH1/TC1 cells secreting interleukin-2/interferon- (IL-2/IFN-) or TH2/TC2 cells secreting IL-4/IL-5/IL-10. In vivo, allogeneic T1 cells expanded, maintained T1 secretion, and acquired allospecificity involving IFN- and IL-5. In contrast, allogeneic T2 cells expanded less and maintained T2 secretion but did not develop significant allospecificity.Allogeneic, but not syngeneic, T1 cells mediated a GVT effect against host-type breast cancer cells, as median survival time (MST) increased from 25.6 ± 2.6 (tumor controls) to 69.2 ± 5.9 days (P < 1.2 x 10-9). This T1-associated GVT effect operated independently of fasL because T1 cells from gld mice mediated tumor-free survival. In contrast, allogeneic T2 cells mediated a modest, noncurative GVT effect (MST, 29 ± 1.3 days; P < .0019). T1 recipients had moderate GVHD (histologic score, 4 of 12) that contributed to lethality after bone marrow transplantation; in contrast, T2 recipients had minimal GVHD (histologic score, 1 of 12). CD3/CD28 co-stimulation, therefore, generates T1 or T2 populations with differential in vivo capacity for expansion to alloantigen, resulting in differential GVT effects and GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Mariotti, J. Foley, K. Ryan, N. Buxhoeveden, V. Kapoor, S. Amarnath, and D. H. Fowler Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an interleukin-4/STAT6 pathway Blood, December 1, 2008; 112(12): 4765 - 4775. [Abstract] [Full Text] [PDF] B. Vasir, Z. Wu, K. Crawford, J. Rosenblatt, C. Zarwan, A. Bissonnette, D. Kufe, and D. Avigan Fusions of Dendritic Cells with Breast Carcinoma Stimulate the Expansion of Regulatory T Cells while Concomitant Exposure to IL-12, CpG Oligodeoxynucleotides, and Anti-CD3/CD28 Promotes the Expansion of Activated Tumor Reactive Cells J. Immunol., July 1, 2008; 181(1): 808 - 821. [Abstract] [Full Text] [PDF] J. Mariotti, J. Foley, U. Jung, T. Borenstein, N. Kantardzic, S. Han, J. T. Hanson, E. Wong, N. Buxhoeveden, J. B. Trepel, et al. Ex Vivo Rapamycin Generates Apoptosis-Resistant Donor Th2 Cells That Persist In Vivo and Prevent Hemopoietic Stem Cell Graft Rejection J. Immunol., January 1, 2008; 180(1): 89 - 105. [Abstract] [Full Text] [PDF] S.-J. Liu, J.-P. Tsai, C.-R. Shen, Y.-P. Sher, C.-L. Hsieh, Y.-C. Yeh, A.-H. Chou, S.-R. Chang, K.-N. Hsiao, F.-W. Yu, et al. Induction of a distinct CD8 Tnc17 subset by transforming growth factor-{beta} and interleukin-6 J. Leukoc. Biol., August 1, 2007; 82(2): 354 - 360. [Abstract] [Full Text] [PDF] B. W. Blaser, N. R. Schwind, S. Karol, D. Chang, S. Shin, S. Roychowdhury, B. Becknell, A. K. Ferketich, D. F. Kusewitt, B. R. Blazar, et al. Trans-presentation of donor-derived interleukin 15 is necessary for the rapid onset of acute graft-versus-host disease but not for graft-versus-tumor activity Blood, October 1, 2006; 108(7): 2463 - 2469. [Abstract] [Full Text] [PDF] J. E. Foley, U. Jung, A. Miera, T. Borenstein, J. Mariotti, M. Eckhaus, B. E. Bierer, and D. H. Fowler Ex Vivo Rapamycin Generates Donor Th2 Cells That Potently Inhibit Graft-versus-Host Disease and Graft-versus-Tumor Effects via an IL-4-Dependent Mechanism J. Immunol., November 1, 2005; 175(9): 5732 - 5743. [Abstract] [Full Text] [PDF] B. R Blazar and W. J Murphy Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD) Phil Trans R Soc B, September 29, 2005; 360(1461): 1747 - 1767. [Abstract] [Full Text] [PDF] A. A. Erdmann, Z.-G. Gao, U. Jung, J. Foley, T. Borenstein, K. A. Jacobson, and D. H. Fowler Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo Blood, June 15, 2005; 105(12): 4707 - 4714. [Abstract] [Full Text] [PDF] M. R. Bishop, D. H. Fowler, D. Marchigiani, K. Castro, C. Kasten-Sportes, S. M. Steinberg, J. C. Gea-Banacloche, R. Dean, C. K. Chow, C. Carter, et al. Allogeneic Lymphocytes Induce Tumor Regression of Advanced Metastatic Breast Cancer J. Clin. Oncol., October 1, 2004; 22(19): 3886 - 3892. [Abstract] [Full Text] [PDF]

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