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International Immunology Advance Access originally published online on March 28, 2006
International Immunology 2006 18(5):719-728; doi:10.1093/intimm/dxl009
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC

Tara M Strutt1,3,, Jude Uzonna2, Karl K McKinstry1,3, and Peter A Bretscher1

1 Department of Microbiology and Immunology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada
2 Department of Immunology, University of Manitoba, Winnipeg, Manitoba, R3E OW3, Canada
3 Present address: Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983, USA

Correspondence to: P. Bretscher; E-mail: bretschr{at}duke.usask.ca

We examine here the in vitro requirements to activate immunocompetent T cells, present among thymocytes, to give rise to CTL, CD4+ T cells producing IL-2 and CD8+ T cells producing IFN-{gamma}. These thymocytes are naive in not having received antigen-dependent signals characteristic of the periphery. Their activation, upon stimulation with allogeneic spleen cells depleted of T cells, referred to here as allogeneic antigen-presenting cells (APCs), to produce allo-MHC-specific effector T cells, requires activated (radiation resistant) CD4+ T cells, syngeneic with the responding thymocytes. We refer here to these T cells as ‘help’. Furthermore, optimal T cell activation requires an Ig+ B220+ cell in the allogeneic APC population, most probably a B cell. The allogeneic APCs cannot be replaced by conventional bone marrow (BM)-derived dendritic cells (DCs) activated by CD40 ligation or exposure to LPS. The requirements for both help and allogeneic B cells in the activation of thymocytes contrast with the requirements to generate substantial responses from splenic T cell populations. Activated, BM-derived DCs stimulate substantial splenic responses without help. These different requirements for activation could reflect the fact that thymocytes have not received an exit-thymus signal and/or that splenic T cells are heterogeneous, containing naive, memory and partially-activated T cells.

Keywords: B cells, cytotoxic T cells, thymocyte activation

Transmitting editor: A. Singer


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