T-cell developmental blockage by tachykinin antagonists and the role of hemokinin 1 in T lymphopoiesis.
Hemokinin 1 (HK-1) is a new member of the tachykinin peptide family that is expressed in hematopoietic 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 (FTOCs). 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 we previously reported for B-cell development. Consistent with this, the detrimental effect of tachykinin antagonists could be partially overcome with exogenous HK-1 peptide.
Zhang
Yu
Y
Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. zhangyu@uhnres.utoronto.ca
Paige
Christopher J
CJ
D000818:Animals; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D005260:Female; D005333:Fetus; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009924:Organ Culture Techniques; D011247:Pregnancy; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015320:Tachykinins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology
D011498:Protein Precursors; D012333:RNA, Messenger; C486037:TAC4 protein, human; C423233:Tac4 protein, mouse; D015320:Tachykinins; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D014364:Tryptophan