Human interferon-inducible protein-10 induces mononuclear cell infiltration in mice and promotes the migration of human T lymphocytes into the peripheral tissues of human peripheral blood lymphocytes-SCID mice

Dennis D. Taub, Dan L. Longo, William J Murphy

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Abstract

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 α subfamily of chemotactic cytokines called chemokines (Taub and Oppenheim, Cytokine 5:175, 1993). However, in contrast to other α 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 (rhlP-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 (108 cells), followed by a subcutaneous injection of rhlP-10 (1 μg/injection) in the hind flank for 4 hours or sequential injections for 3 days. The skin and underlying tissue from the rhlP-10 injection site were then biopsied and examined for the extent of mononuclear cell infiltration. rhlP-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 rhlP-10 injections. These results show that rhlP-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.

Original languageEnglish (US)
Pages (from-to)1423-1431
Number of pages9
JournalBlood
Volume87
Issue number4
StatePublished - Feb 15 1996
Externally publishedYes

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Chemokine CXCL10
Severe Combined Immunodeficiency
T-cells
Lymphocytes
Infiltration
Blood
Tissue
T-Lymphocytes
Chemokines
Injections
Proteins
Monocytes
Subcutaneous Injections
Cytokines
Endothelial cells
Glycoproteins
Skin
Intraperitoneal Injections
Keratinocytes
Astrocytes

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Human interferon-inducible protein-10 induces mononuclear cell infiltration in mice and promotes the migration of human T lymphocytes into the peripheral tissues of human peripheral blood lymphocytes-SCID mice",
abstract = "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 α subfamily of chemotactic cytokines called chemokines (Taub and Oppenheim, Cytokine 5:175, 1993). However, in contrast to other α 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 (rhlP-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 (108 cells), followed by a subcutaneous injection of rhlP-10 (1 μg/injection) in the hind flank for 4 hours or sequential injections for 3 days. The skin and underlying tissue from the rhlP-10 injection site were then biopsied and examined for the extent of mononuclear cell infiltration. rhlP-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 rhlP-10 injections. These results show that rhlP-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.",
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T1 - Human interferon-inducible protein-10 induces mononuclear cell infiltration in mice and promotes the migration of human T lymphocytes into the peripheral tissues of human peripheral blood lymphocytes-SCID mice

AU - Taub, Dennis D.

AU - Longo, Dan L.

AU - Murphy, William J

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N2 - 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 α subfamily of chemotactic cytokines called chemokines (Taub and Oppenheim, Cytokine 5:175, 1993). However, in contrast to other α 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 (rhlP-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 (108 cells), followed by a subcutaneous injection of rhlP-10 (1 μg/injection) in the hind flank for 4 hours or sequential injections for 3 days. The skin and underlying tissue from the rhlP-10 injection site were then biopsied and examined for the extent of mononuclear cell infiltration. rhlP-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 rhlP-10 injections. These results show that rhlP-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.

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