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Human interferon-inducible protein-10 induces mononuclear cell infiltration
in mice and promotes the migration of human T lymphocytes into the
peripheral tissues and human peripheral blood lymphocytes-SCID mice
DD Taub, DL Longo and WJ Murphy
Clinical Services Program, SAIC, Frederick, MD 21702-1201, USA.
The human cytokine, interferon-inducible protein-10 (IP-10), is a small
glycoprotein secreted by activated monocytes, T cells, keratinocytes,
astrocytes, and endothelial cells and is structurally related to the alpha
subfamily of chemotactic cytokines called chemokines (Taub and Oppenheim,
Cytokine 5:175, 1993). However, in contrast to other alpha chemokines that
induce neutrophil migration, IP-10 has been shown to chemoattract monocytes
and T lymphocytes in vitro, suggesting a role in T-cell-mediated immune
responses. We therefore examined the effects of human IP-10 after in vivo
administration. IP-10 induces significant mononuclear cell infiltration
after subcutaneous injections in normal mice. In an effort to study the in
vivo effects of IP-10 on human leukocyte migration, we then examined the
ability of recombinant human IP-10 (rhIP-10) to induce human-T-cell
infiltration using a human/severe combined immune deficiency (SCID) mouse
model. SCID mice received an intraperitoneal injection of human peripheral
blood lymphocytes (10(8) cells), followed by a subcutaneous injection of
rhIP- 10 (1 micrograms/injection) in the hind flank for 4 hours or
sequential injections for 3 days. The skin and underlying tissue from the
rhIP-10 injection site were then biopsied and examined for the extent of
mononuclear cell infiltration. rhIP-10 again induced significant
mononuclear cell accumulation 72 hours after injection. Immunohistologic
evaluation determined that a significant number of human CD3+ T cells were
recruited in response to rhIP-10 injections. These results show that
rhIP-10 is capable of inducing human T-cell migration in vivo and may play
an important role in monocyte and lymphocyte recruitment into inflammatory
sites.
Volume 87,
Issue 4,
pp. 1423-1431,
02/15/1996
Copyright © 1996 by The American Society of Hematology
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