Modulation of IL-8 receptor expression on purified human T lymphocytes is associated with changed chemotactic responses to IL-8.
Interleukin-8 is a member of the chemokine superfamily and is a major mediator of acute inflammation. Although IL-8 has been reported by some laboratories also to be a chemoattractant for T lymphocytes, this has been difficult to confirm and remains a controversial issue. By using freshly purified human T cells (90-95% CD3+), we could demonstrate consistent directional migration of T cells to recombinant human IL-8. IL-8 was as potent as RANTES, MIP1 alpha, and MIP1 beta in inducing T cell chemotaxis. Highly purified T cells, however, incubated at 37 degrees C for more than 12 h or cultured overnight with anti-CD3 antibody cross-linked to plastic dishes, showed a markedly reduced capacity to migrate in response to IL-8. This was associated with a decrease in binding of radioiodinated IL-8 to T cells. Northern blot and polymerase chain reaction analyses showed that freshly purified T cells expressed mRNA for both IL-8 receptor type A and type B. Steady-state levels of mRNA for the IL-8RA and IL-8RB genes were also reduced by incubation of the cells with or without anti-CD3 for 12 h at 37 degrees C. These results indicate that T cells are indeed one of the target cell populations for IL-8. The regulation of IL-8 receptor expression on T lymphocytes may contribute to the pathophysiological role of IL-8 in inducing the homing and infiltration of T cells.
Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
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L
Xu
D J
DJ
Kelvin
G Q
GQ
Ye
D D
DD
Taub
A
A
Ben-Baruch
J J
JJ
Oppenheim
J M
JM
Wang
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002846:Chromatography, Affinity; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018123:Receptors, Interleukin / Q000502:physiology*; D023062:Receptors, Interleukin-8A; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D002630:Chemotactic Factors; D016209:Interleukin-8; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A