Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1.
Activated T lymphocytes differentiate into effector cells tailored to meet disparate challenges to host integrity. For example, type 1 and type 2 helper (T(H)1 and T(H)2) cells secrete cytokines that enhance cell-mediated and humoral immunity, respectively. The chemokine monocyte chemoattractant protein-1 (MCP-1) can stimulate interleukin-4 production and its overexpression is associated with defects in cell-mediated immunity, indicating that it might be involved in T(H)2 polarization. Here we show that MCP-1-deficient mice are unable to mount T(H)2 responses. Lymph node cells from immunized MCP-1(-/-) mice synthesize extremely low levels of interleukin-4, interleukin-5 and interleukin-10, but normal amounts of interferon-gamma and interleukin-2. Consequently, these mice do not accomplish the immunoglobulin subclass switch that is characteristic of T(H)2 responses and are resistant to Leishmania major. These effects are direct rather than due to abnormal cell migration, because the trafficking of naive T cells is undisturbed in MCP-1(-/-) mice despite the presence of MCP-1-expressing cells in secondary lymphoid organs of wild-type mice. Thus, MCP-1 influences both innate immunity, through effects on monocytes, and adaptive immunity, through control of T helper cell polarization.
Gu
L
L
Department of Adult Oncology, Dana-Farber Cancer Institute, Brigham & Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Tseng
S
S
Horner
R M
RM
Tam
C
C
Loda
M
M
Rollins
B J
BJ
D000818:Animals; D018932:Chemokine CCL2 / Q000172:deficiency / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D007109:Immunity; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D018932:Chemokine CCL2; D016207:Cytokines; D007074:Immunoglobulin G; D015847:Interleukin-4