Control of Immune Responses by Naturally Arising CD4⁺ Regulatory T Cells That Express Toll-like Receptors

It is a key issue in immunology to understand how the immune system discriminates between self- and nonself, inhibiting autoimmune responses but allowing the host to mount immune responses against invading microbes (1–3). This is due to the fact that once antigen-specific lymphocytes are activated in adaptive immune responses, they exhibit essentially the same effector activity whether they respond to a microbe or to a self-constituent. That is, once aberrant immune responses (e.g., autoimmune, immunopathologic, or allergic responses) are triggered, serious damage to the host may ensue because of the power of potent effector activity, high antigen specificity, and immunologic memory of adaptive immunity. There is now accumulating evidence in humans and animals that the normal immune system harbors naturally arising CD4⁺ regulatory T (T_R) cells, which play key roles in controlling such aberrant immune responses (4...