Anti-tumor immunity and autoimmunity: a balancing act of regulatory T cells.
Regulatory T (Treg) cell activity has been observed in anti-tumor and autoimmunity since the 1970s. Functional and molecular characterization of Treg cells has been made possible by the recent association of cell markers, such as CD25, CTLA-4, GITR, and Foxp3 gene product, with immunoregulatory activity. Here the influence of Treg cells in both anti-tumor immunity and autoimmunity was measured in BALB/c mice. Depletion of CD4(+)CD25(+) Treg cells with CD25 mAb resulted in mammary tumor regression and increased susceptibility to thyroiditis. This in vivo priming to both tumor-associated antigens and self-thyroglobulin attests to the presence of otherwise undetectable immune effectors which are under negative regulation. Modulation of Treg cells is a powerful strategy in cancer therapy, but may potentiate autoimmune complications. Murine models exhibiting breakable tolerance to tumor-associated antigens, such as ErbB-2 (HER-2/ neu), and increased susceptibility to autoimmunity following Treg-cell depletion are being established to test new vaccination or therapeutic strategies involving Treg-cell modulation.
Wei
Wei-Zen
WZ
Karmanos Cancer Institute, Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201, USA. weiw@wayne.edu
Morris
Gerald P
GP
Kong
Yi-Chi M
YC
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis / Q000502:physiology; D000951:Antigens, Neoplasm / Q000276:immunology*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D008212:Lymphocyte Depletion; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013954:Thyroglobulin / Q000378:metabolism; D013966:Thyroiditis / Q000209:etiology
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D013954:Thyroglobulin