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

William J Murphy, Zhi Gang Tian, Osamu Asai, Satoshi Funakoshi, Poppy Rotter, Michelle Henry, Robert M. Strieter, Steven L. Kunkel, Dan L. Longo, Dennis D. Taub

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55 Scopus citations

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-1α (rhMIP-1α), 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-1β to induce human T cell infiltration into injection sites in human PBL-SCID mice. SCID mice received s.c. injections of rhMIP-1β or PBS (1 μg/injection) in the hindflank for 4 h or sequential injections for 3 days. Biopsies of the MIP-1β 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-1β injections, and this infiltration could be specifically blocked by co-administration of anti-MIP- 1β 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-1β 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-1β with anti-MIP-1β antiserum abrogated the increase in T cell homing to the thymus. These data demonstrate that MIP-1β 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.

Original languageEnglish (US)
Pages (from-to)2104-2111
Number of pages8
JournalJournal of Immunology
Volume156
Issue number6
StatePublished - Mar 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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