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Chemokines and T lymphocyte activation: II. Facilitation of human T cell trafficking in severe combined immunodeficiency mice.

W J Murphy, Z G Tian, O Asai, S Funakoshi, P Rotter, M Henry, R M Strieter, S L Kunkel, D L Longo and D D Taub
J Immunol March 15, 1996, 156 (6) 2104-2111;
W J Murphy
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Z G Tian
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O Asai
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S Funakoshi
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P Rotter
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M Henry
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R M Strieter
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S L Kunkel
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D L Longo
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D D Taub
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Abstract

Previous studies from this laboratory have demonstrated that the chemokines RANTES (recombinant human regulated upon activation, normally T cell expressed and presumably secreted), macrophage chemotactic peptide-1, recombinant human macrophage inflammatory protein-1 alpha (rhMIP-1 alpha) IL-8, and IP-10 are capable of inducing human T cell infiltration into the injection site of severe combined immunodeficiency (SCID) mice reconstituted with human PBL. However, the ability of these chemokines to facilitate T cell homing into various lymphoid tissues has not been examined. Initial studies focused on the ability of rhMIP-1 beta to induce human T cell infiltration into injection sites in human PBL-SCID mice. SCID mice received s.c. injections of rhMIP-1 beta or PBS (1 microgram/injection) in the hindflank for 4 h or sequential injections for 3 days. Biopsies of the MIP-1 beta injection site revealed the presence of significant mononuclear cell accumulation 72 h after injection. Immunohistologic evaluation determined that significant numbers of human CD3+ T cells were recruited in response to MIP-1 beta injections, and this infiltration could be specifically blocked by co-administration of anti-MIP-1 beta antiserum. We subsequently examined these chemokine-injected mice for the effect of trafficking of human T cells to peripheral lymphoid organs. Flow cytometric analysis of the thymus in human PBL-SCID mice revealed that treatment with rhMIP-1 beta or rhRANTES, but not platelet factor-4, resulted in improved thymic homing of the human T cells after 72 h. This trafficking effect was shown to be direct, as pretreatment of the human T cells with the chemokines in vitro also improved peripheral lymphoid trafficking of the human cells. In addition, co-injection of rhMIP-1 beta with anti-1 beta antiserum abrogated the increase in T cell homing to the thymus. These data demonstrate that MIP-1 beta and RANTES directly augment human T cell trafficking to peripheral murine lymphoid tissues. Chemokines may, therefore, under either isogeneic or xenogeneic conditions, play a role in normal lymphocyte recirculation and homing, and may be of potential clinical use in promoting immune cell trafficking and function.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 156, Issue 6
15 Mar 1996
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Chemokines and T lymphocyte activation: II. Facilitation of human T cell trafficking in severe combined immunodeficiency mice.
W J Murphy, Z G Tian, O Asai, S Funakoshi, P Rotter, M Henry, R M Strieter, S L Kunkel, D L Longo, D D Taub
The Journal of Immunology March 15, 1996, 156 (6) 2104-2111;

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Chemokines and T lymphocyte activation: II. Facilitation of human T cell trafficking in severe combined immunodeficiency mice.
W J Murphy, Z G Tian, O Asai, S Funakoshi, P Rotter, M Henry, R M Strieter, S L Kunkel, D L Longo, D D Taub
The Journal of Immunology March 15, 1996, 156 (6) 2104-2111;
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Print ISSN 0022-1767        Online ISSN 1550-6606