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Regulation of activities of NK cells and CD4 expression in T cells by human HNP-1, -2, and -3

Authors
  • Zhang, Kun
  • Lu, Qinghua
  • Zhang, Qian
  • Hu, Xun
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Publication Date
Jan 01, 2004
Volume
323
Issue
2
Pages
437–444
Identifiers
DOI: 10.1016/j.bbrc.2004.08.111
Source
Elsevier
Keywords
License
Unknown

Abstract

Human neutrophil defensin α (HNP) is a group of cationic peptides of diverse physiological roles. Recent studies revealed the nature of HNPs as the dominant HLA-DR binding peptides on malignant cancer cells, which may block the major histocompatibility complex for antigen presentation. Here we show that HNPs may inhibit T cells by downregulating CD4 expression, a molecule of critical importance for T cell’s interaction with the target cell. HNPs also inhibited tumor-cell-lysis activities of NK cells by downregulating CD16–CD56 expression. More importantly, HNPs were markedly elevated in 14 cancer tissues out of 15 self-paired human colorectal cancers and their adjacent noncancerous tissues. The subset compositions of HNPs extracted from cancer tissues and neutrophils were identical. Immunohistochemical studies indicated that HNPs mainly distributed in the infiltrated neutrophils in the interstitium. The elevated HNPs in cancer tissues may create a microenvironment unfavorable for adaptive immune reaction, implicating the cancer evasion.

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