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Blood, 30 April 2009, Vol. 113, No. 18, pp. 4273-4280. Prepublished online as a Blood First Edition Paper on January 12, 2009; DOI 10.1182/blood-2008-09-181263. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-09-181263v1 113/18/4273    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 Citing Articles via Google Scholar Google Scholar Articles by Ryu, S. J. Articles by Choi, E. Y. Search for Related Content PubMed PubMed Citation Articles by Ryu, S. J. Articles by Choi, E. Y. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Cognate CD4 help is essential for the reactivation and expansion of CD8 memory T cells directed against the hematopoietic cell–specific dominant minor histocompatibility antigen, H60 Su Jeong Ryu1,*, Kyung Min Jung2,*, Hyun Seung Yoo1, Tae Woo Kim3, Sol Kim4, Jun Chang4, and Eun Young Choi1,2 1 Department of Biomedical Sciences, and 2 Graduate Program of Immunology, Seoul National University College of Medicine, Seoul; 3 Graduate School of Medicine, Korea University, Seoul; and 4 Division of Life and Pharmaceutical Sciences, Ewha Woman's University, Seoul, Korea In contrast to previous notions of the help-independency of memory CD8 T cells during secondary expansion, here we show that CD4 help is indispensable for the re-expansion of once-helped memory CD8 T cells, using a hematopoietic cell–specific dominant minor histocompatibility (H) antigen, H60, as a model antigen. H60-specific memory CD8 T cells generated during a helped primary response vigorously expanded only when rechallenged under helped conditions. The help requirement for an optimal secondary response was confirmed by a reduction in peak size by CD4 depletion, and was reproduced after skin transplantation. Helpless conditions or noncognate separate help during the secondary response resulted in a significant reduction in the peak size and different response kinetics. Providing CD4 help again during a tertiary challenge restored robust memory expansion; however, the repeated deprivation of help further reduced clonal expansion. Adoptively transferred memory CD8 T cells did not proliferate in CD40L–/– hosts. In the CD40–/– hosts, marginal memory expansion was detected after priming with male H60 cells but was completely abolished by priming with peptide-loaded CD40–/– cells, suggesting the essential role of CD40 and CD40L in memory responses. These results provide insight into the control of minor H antigen-specific CD8 T-cell responses, to maximize the graft-versus-leukemia response. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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