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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1960-1969.
Prepublished online as a Blood First Edition Paper on May 17, 2007; DOI 10.1182/blood-2006-09-045807.
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Submitted September 5, 2006
Accepted May 11, 2007
Bone marrow CD8 cells down-modulate membrane IL-7R expression and exhibit increased STAT-5 and p38 MAPK phosphorylation in the organ environment
Giuliana Cassese, Elisabetta Parretta, Laura Pisapia, Angela Santoni, John Guardiola, and Francesca Di Rosa*
Institute of Genetics and Biophysics, "Adriano Buzzati-Traverso", Consiglio Nazionale delle Ricerche, Naples, Italy
Department of Experimental Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome "La Sapienza", Rome, Italy
Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche, Rome, Italy
* Corresponding author; email: dirosa{at}igb.cnr.it.
By comparing mature CD8 cell turn-over in different organs, we previously demonstrated that CD8 cells proliferate predominantly in the bone marrow (BM). To investigate the mechanisms underlying such increased turn-over, we compared here BM, lymph nodes (LN) and spleen CD8 cells from untreated C57BL/6 mice as regards in vivo proliferation within the organ; in vitro response to IL-7, IL-15, IL-21; ex vivo expression of membrane CD127 (IL-7R ), intra-cellular Bcl-2, phospho-STAT-5, phospho-p38 MAPK; in vivo proliferation upon adoptive transfer. Into the BM, the proliferation rate was increased for either total CD8 cells or individual CD44 and CD122 subsets. In contrast, purified CD8+ cells from the BM did not show an enhanced in vitro proliferative response to IL-7, IL-15, IL-21 as compared to corresponding spleen cells. After transfer and polyI:C treatment, both spleen- and BM-derived CD8 cells from congenic donors proliferated about 2-times more in the recipient BM than in spleen and LN. Our results suggest that BM CD8 cells are not committed to self-renewal, but rather are stimulated in the organ. Molecular events constantly induced in the CD8 cells within the BM of untreated mice include increase of both phosphorylated STAT-5 and phosphorylated p38 intracellular levels, reduction of CD127 membrane expression.

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E. Parretta, G. Cassese, A. Santoni, J. Guardiola, A. Vecchio, and F. Di Rosa
Kinetics of In Vivo Proliferation and Death of Memory and Naive CD8 T Cells: Parameter Estimation Based on 5-Bromo-2'-Deoxyuridine Incorporation in Spleen, Lymph Nodes, and Bone Marrow
J. Immunol.,
June 1, 2008;
180(11):
7230 - 7239.
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