Control of T(H)2 polarization by the chemokine monocyte chemoattractant protein-1

Activated T lymphocytes differentiate into effector cells tailored to meet disparate challenges to host integrity(1). For example, type 1 and type 2 h elper (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(2) and its overexp ression is associated with defects in cell-mediated immunity(3), indicating that it might be involved in T(H)2 polarization. Here we show that MCP-1-d eficient mice are unable to mount T(H)2 responses. Lymph node cells from im munized MCP-1(-/-) mice synthesize extremely low levels of interleukin-4, i nterleukin-5 and interleukin-10, but normal amounts of interferon-gamma and interleukin-2. Consequently, these mice do not accomplish the immunoglobul in subclass switch that is characteristic of T(H)2 responses and are resist ant to Leishmania major. These effects are direct rather than due to abnorm al cell migration, because the trafficking of naive T cells is undisturbed in MCP-1(-/-) mice despite the presence of MCP-1-expressing cells in second ary lymphoid organs of wild-type mice. Thus, MCP-1 influences both innate i mmunity, through effects on monocytes, and adaptive immunity, through contr ol of T helper cell polarization.