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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2002-11-3572.

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Submitted November 26, 2002
Accepted May 16, 2003

T cell developmental blockage by tachykinin antagonists and the role of hemokinin 1 in T lymphopoiesis

Yu Zhang* and Christopher J Paige

Ontario Cancer Institute, Princess Margaret Hospital, University Health Network and Department of Medical Biophysics and Immunology, University of Toronto, Toronto, ON, Canada

* Corresponding author; email: zhangyu{at}oci.utoronto.ca.

Hemokinin 1 (HK-1) is a new member of the tachykinin peptide family that is expressed in hemopoietic cells. Recent reports studying mouse, rat, and human orthologs of HK-1 demonstrate a broader distribution than originally reported. Our previous studies demonstrated that HK-1, by promoting proliferation, survival, and possibly maturation of B cell precursors, plays an important role in B lymphopoiesis. Here we present data showing that HK-1 also influences T cell development at a similar stage of differentiation. This peptide enhanced the proliferation of T cell precursors, and increased the number of thymocytes in fetal thymus organ cultures (FTOC). Tachykinin antagonists, on the other hand, greatly reduced the cellularity of thymi both in vivo and in vitro. The major reduction occurred in the CD4/CD8 double positive (DP) cells and the CD44-CD25+ subset of the CD4/CD8 double negative (DN) cells. Of note, these populations also express HK-1, raising the possibility of autocrine or paracrine pathways influencing T cell development as previously we reported for B cell development. Consistent with this, the detrimental effect of tachykinin antagonists could be partially overcome with exogenous HK-1 peptide.


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