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Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1

Nature volume 404, pages 407–411 (2000)Cite this article

Abstract

Activated T lymphocytes differentiate into effector cells tailored to meet disparate challenges to host integrity1. For example, type 1 and type 2 helper (TH1 and TH2) cells secrete cytokines that enhance cell-mediated and humoral immunity, respectively. The chemokine monocyte chemoattractant protein-1 (MCP-1) can stimulate interleukin-4 production2 and its overexpression is associated with defects in cell-mediated immunity3, indicating that it might be involved in TH2 polarization. Here we show that MCP-1-deficient mice are unable to mount TH2 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-γ and interleukin-2. Consequently, these mice do not accomplish the immunoglobulin subclass switch that is characteristic of TH2 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.

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Figure 1: Effect of MCP-1 on cytokine synthesis.
Figure 2: Effect of MCP-1 on IgG subclass concentrations.
Figure 3: Resistance of MCP-1-/- mice to Leishmania major.
Figure 4: Effect of MCP-1 on T-lymphocyte trafficking.
Figure 5: Expression of MCP-1 in spleen and lymph nodes.

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Acknowledgements

We thank A. Abbas, C. Gerard, R. Ransohoff and E. Reinherz for helpful comments and advice; P. Marks, L. Clayton and C. Daly for assistance; A. Satoskar and J. David for Leishmania major; and the staff of the Animal Resource Facility at Dana-Farber Cancer Institute for their humane animal care. Supported by NIH grants to B.J.R., who is also a Scholar of the Leukemia Society of America and is supported by the Novartis/Dana-Farber Drug Discovery Program.

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  1. Department of Adult Oncology, Dana-Farber Cancer Institute, Brigham & Women's Hospital, and Harvard Medical School, 44 Binney Street, Boston, 02115, Massachusetts, USA

    Long Gu, Susan Tseng, Renée M. Horner, Carmen Tam, Massimo Loda & Barrett J. Rollins

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Correspondence to Barrett J. Rollins.

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Gu, L., Tseng, S., Horner, R. et al. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404, 407–411 (2000). https://doi.org/10.1038/35006097

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