Human RANTES induces the migration of human T lymphocytes into the peripheral tissues of mice with severe combined immune deficiency
- 1 August 1994
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 24 (8), 1823-1827
- https://doi.org/10.1002/eji.1830240815
Abstract
The human cytokine, Recombinant Human Regulated on Activation, Normal T Expressed and Secreted (rhRANTES), is a small glycoprotein secreted by activated T cells and platelets and is structurally related to a family of chemotactic cytokines called chemokines. Evaluation of the effects of chemokines on human cells has largely been limited to in vitro binding assays. In an effort to study the in vivo effects of chemokines on human leukocyte migration, we examined the ability of rhRANTES to induce human T cell infiltration using a human/severe combined immune deficient (SCID) mouse model. SCID mice received human peripheral blood lymphocytes, followed by sequential subcutaneous injections of rhRANTES in the hind flank for 3 days. The skin and underlying tissue from the rhRANTES injection site were then biopsied and examined for the extent of human mononuclear cell infiltration. rhRANTES induced significant mononuclear cell accumulation 72 h after injection. Immunohistological evaluation determined that the majority of the cells recruited in response to rhRANTES injections were human CD33+ T cells with equal numbers of CD4+ and CD8+ cells. In contrast, subcutaneous injections of recombinant human macrophage colony-stimulating factors resulted in little human cellular infiltration. Murine mononuclear cell infiltration in response to rhRANTES was also present suggesting that the in vivo effects of rhRANTES may be both direct and indirect. These results demonstrate that rhRANTES induces significant human T cell migration in vivo and suggests that the human/SCID mouse model may provide an important tool in studying the in vivo effects of chemokines on human leukocytes and leukocyte subsets.Keywords
This publication has 13 references indexed in Scilit:
- Preferential Migration of Activated CD4 + and CD8 + T Cells in Response to MIP-1α and MIP-1βScience, 1993
- Human/severe combined immunodeficient mouse chimeras. An experimental in vivo model system to study the regulation of human endothelial cell-leukocyte adhesion molecules.JCI Insight, 1993
- RANTES and macrophage inflammatory protein 1 alpha induce the migration and activation of normal human eosinophil granulocytes.The Journal of Experimental Medicine, 1992
- Human‐mouse lymphoid chimeras: host‐vs.‐graft and graft‐vs.‐host reactionsEuropean Journal of Immunology, 1992
- Biology of the rantes/sis cytokine familyCytokine, 1991
- Properties of the Novel Proinflammatory Supergene "Intercrine" Cytokine FamilyAnnual Review of Immunology, 1991
- Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTESNature, 1990
- Properties of monocyte chemotactic and activating factor (MCAF) purified from a human fibrosarcoma cell line.The Journal of Experimental Medicine, 1990
- The SCID-hu Mouse: Murine Model for the Analysis of Human Hematolymphoid Differentiation and FunctionScience, 1988
- Transfer of a functional human immune system to mice with severe combined immunodeficiencyNature, 1988