Naturally occurring CD4 regulatory T cells (TR) that express CD25 and the transcription factor FoxP3 play a key role in immune homeostasis, preventing immune pathological responses to self and foreign Ags. CTLA-4 is expressed by a high percentage of these cells, and is often considered as a marker for TR in experimental and clinical ysis. However, it has not yet been proven that CTLA-4
has a direct role in TR function. In this study, using a T cell-mediated colitis model,
we demonstrate that anti-CTLA-4 mAb treatment inhibits TR function in vivo via direct effects on CTLA-4-expressing TR, and not via hyperactivation of colitogenic effector T cells. Although anti-CTLA-4 mAb treatment completely inhibits TR function, it does not reduce TR numbers or their homing to the GALT, suggesting the Ab mediates its function by blockade of a signal required for TR activity.
In contrast to the striking effect of the Ab, CTLA-4-deficient mice can produce functional TR, suggesti-ing that under some circumstances other immune regulatory mechanis, including the production of IL-10, are able to compensate for the loss of the CTLA-4-mediated pathway. This study provides direct evidence that CTLA-4 has a specific, nonredundant role in the function of normal TR. This
role has to be taken into account when targeting CTLA-4 for therapeutic purposes, as such a strategy will not only boost effector T cell responses, but might also break TR-mediated self-tolerance. The Journal of Immunology, 2006, 177: 4376–4383.仅翻译彩色文字的一句话即可，谢谢，急等
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