Chemokines and T lymphocyte activation: II. Facilitation of human T cell trafficking in severe combined immunodeficiency mice.
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.
Murphy
W J
WJ
Biological Carcinogenesis and Development Program, Science Applications International Corporation-Frederick, MD 21702 USA.
Tian
Z G
ZG
Asai
O
O
Funakoshi
S
S
Rotter
P
P
Henry
M
M
Strieter
R M
RM
Kunkel
S L
SL
Longo
D L
DL
Taub
D D
DD
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D018925:Chemokines / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation / Q000187:drug effects*; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D016513:Mice, SCID; D015846:Monokines / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011994:Recombinant Proteins