IL-8-induced T-lymphocyte migration: Direct as well as indirect mechanisms

Ji Ming Wang, Xu Luoling, William J Murphy, Dennis D. Taub, Oleg Chertov

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Although IL-8 has been reported to be a chemoattractant for T cells in vivo and in vitro, this has been a controversial issue. By using freshly purified human T cells (> 90% CD3+), we demonstrated consistent T-cell migration in response to recombinant human IL-8 in vitro. However, highly purified T cells, when incubated at 37°C for more than 12 h or cultured overnight in the presence of anti-CD3 antibody, showed a markedly reduced capacity to migrate in response to IL-8. This reduction in chemotaxis was associated with a decrease in binding of 125I-IL-8 to T cells. Northern blots showed that freshly purified T cells expressed both IL-8 receptor type A and type B transcripts. Steady-state levels of mRNA for IL-8RA and IL-8RB in T cells were progressively reduced with time by incubation of the cells at 37°C with or without anti-CD3. The inability of cultured T cells to migrate in response to IL-8 accounts for the contradictory published reports on this issue. In vivo administration of IL-8 in rats resulted in the infiltration at the injection site of neutrophils followed by T cells, and this later T-cell infiltration was reported to be partially blocked by selective depletion of neutrophils. These observations raised the possibility that IL-8 may trigger neutrophils to release a factor(s) that may also participate in the T-cell recruitment. Neutrophil granule proteins, defensins, and CAP37/azurocidin released upon stimulation of cells by IL-8 were shown to induce human T-cell migration in vitro. Subcutaneous injection of defensins into SCID mice engrafted with human PBL resulted in significant infiltration by human CD3+ T lymphocytes. These results indicate that IL-8 is able not only to act directly and induce migration of T lymphocytes that express IL-8 receptors, but also to act indirectly by activating neutrophils to release additional T-cell chemoattractants.

Original languageEnglish (US)
Pages (from-to)135-144
Number of pages10
JournalMethods: A Companion to Methods in Enzymology
Volume10
Issue number1
DOIs
StatePublished - Aug 1996
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)

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