CD4+ CD25high regulatory cells in human peripheral blood

C Baecher-Allan, JA Brown, GJ Freeman… - The Journal of …, 2001 - journals.aai.org
C Baecher-Allan, JA Brown, GJ Freeman, DA Hafler
The Journal of Immunology, 2001journals.aai.org
Thymectomy in mice on neonatal day 3 leads to the development of multiorgan autoimmune
disease due to loss of a CD+ CD25+ T cell regulatory population in their peripheral
lymphoid tissues. Here, we report the identification of a CD4+ population of regulatory T
cells in the circulation of humans expressing high levels of CD25 that exhibit in vitro
characteristics identical with those of the CD4+ CD25+ regulatory cells isolated in mice. With
TCR cross-linking, CD4+ CD25 high cells did not proliferate but instead totally inhibited …
Abstract
Thymectomy in mice on neonatal day 3 leads to the development of multiorgan autoimmune disease due to loss of a CD+ CD25+ T cell regulatory population in their peripheral lymphoid tissues. Here, we report the identification of a CD4+ population of regulatory T cells in the circulation of humans expressing high levels of CD25 that exhibit in vitro characteristics identical with those of the CD4+ CD25+ regulatory cells isolated in mice. With TCR cross-linking, CD4+ CD25 high cells did not proliferate but instead totally inhibited proliferation and cytokine secretion by activated CD4+ CD25− responder T cells in a contact-dependent manner. The CD4+ CD25 high regulatory T cells expressed high levels of CD45RO but not CD45RA, akin to the expression of CD45RB low on murine CD4+ CD25+ regulatory cells. Increasing the strength of signal by providing either costimulation with CD28 cross-linking or the addition of IL-2 to a maximal anti-CD3 stimulus resulted in a modest induction of proliferation and the loss of observable suppression in cocultures of CD4+ CD25 high regulatory cells and CD4+ CD25− responder cells. Whereas higher ratios of CD4+ CD25 high T cells are required to suppress proliferation if the PD-L1 receptor is blocked, regulatory cell function is shown to persist in the absence of the PD-1/PD-L1 or CTLA-4/B7 pathway. Thus, regulatory CD4 T cells expressing high levels of the IL-2 receptor are present in humans, providing the opportunity to determine whether alterations of these populations of T cells are involved in the induction of human autoimmune disorders.
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