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Blood, 1 February 2004, Vol. 103, No. 3, pp. 988-994.
Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-08-2814.


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IMMUNOBIOLOGY

Transregulation of memory CD8 T-cell proliferation by IL-15R{alpha}+ bone marrow–derived cells

Kimberly S. Schluns, Kimberly D. Klonowski, and Leo Lefrançois

From the Division of Immunology, Department of Medicine, University of Connecticut Health Center, Farmington, CT.

Interleukin 15 (IL-15) and the IL-15 receptor {alpha} (IL-15R{alpha}) chain are both required for the basal proliferation of memory CD8 T cells, but which cell types are required to express IL-15 or IL-15R{alpha} to mediate this proliferation is not known. Using bone marrow (BM) chimeras, we showed that virus-specific CD8 memory T-cell proliferation was driven by IL-15 produced by either BM-derived or parenchymal cells. Experiments using mixed BM chimeras showed that IL-15R{alpha} expression by memory CD8 T cells was not required for their division. In addition, wild-type memory CD8 T cells did not divide after transfer into IL-15R{alpha}-/- mice. Further analyses demonstrated that IL-15R{alpha}+ BM-derived cells were crucial in driving memory CD8 T-cell division in the spleen while both parenchymal and BM-derived cells promoted memory cell division in the lung. Proliferation in response to soluble IL-15 in vivo required expression of IL-15R{alpha} by opposing cells and IL-15R{beta} by CD8 memory cells, indicating that IL-15 interacted directly with the T cells. These results indicate that transpresentation of IL-15 by IL-15R{alpha} on BM-derived cells mediates the basal proliferation of memory CD8 T cells. (Blood. 2004;103:988-994)


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