Impaired T cell function in RANTES-deficient mice.
The chemokine RANTES is a chemoattractant for monocytes and T cells and is postulated to participate in many aspects of the immune response. To evaluate the biological roles of RANTES in vivo, we generated RANTES-deficient (-/-) mice and characterized their T cell function. In cutaneous delayed-type hypersensitivity assays, a 50% reduction in ear and footpad swelling was seen in -/- mice compared to +/+ mice. In vitro, polyclonal and antigen-specific T cell proliferation was decreased. Quantitative analysis using the fluorescent dye carboxy-fluorescein succinimidyl ester revealed that this proliferative defect was due both to fewer antigen-reactive T cells and to a reduction in the capacity of these cells to proliferate. In addition, IFN-gamma and IL-2 production by the -/- T cells was dramatically decreased. Together, these data suggest that RANTES is required for normal T cell functions as well as for recruiting monocytes and T cells to sites of inflammation.
Makino
Yasuhiko
Y
Penn Center for Molecular Studies of Kidney Disease, Renal-Electrolyte and Hypertension Division, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Cook
Donald N
DN
Smithies
Oliver
O
Hwang
Olivia Y
OY
Neilson
Eric G
EG
Turka
Laurence A
LA
Sato
Hiroshi
H
Wells
Andrew D
AD
Danoff
Theodore M
TM
D000818:Animals; D015152:Blotting, Northern; D018946:Chemokine CCL5 / Q000172:deficiency* / Q000276:immunology*; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*
D018946:Chemokine CCL5; D007376:Interleukin-2; D007371:Interferon-gamma