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The Journal of Immunology, 2006, 176: 3301-3305.
Copyright © 2006 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: Anti-CD25 Monoclonal Antibody Injection Results in the Functional Inactivation, Not Depletion, of CD4+CD25+ T Regulatory Cells1

Adam P. Kohm*, Jeffrey S. McMahon*, Joseph R. Podojil*, Wendy Smith Begolka*, Mathew DeGutes*, Deborah J. Kasprowicz{dagger}, Steven F. Ziegler{dagger} and Stephen D. Miller2,*

* Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, {dagger} Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101.

CD4+CD25+ T regulatory (TR) cells are an important regulatory component of the adaptive immune system that limit autoreactive T cell responses in various models of autoimmunity. This knowledge was generated by previous studies from our lab and others using TR cell supplementation and depletion. Contrary to dogma, we report here that injection of anti-CD25 mAb results in the functional inactivation, not depletion, of TR cells, resulting in exacerbated autoimmune disease. Supporting this, mice receiving anti-CD25 mAb treatment display significantly lower numbers of CD4+CD25+ T cells but no change in the number of CD4+FoxP3+ TR cells. In addition, anti-CD25 mAb treatment fails to both reduce the number of Thy1.1+ congenic CD4+CD25+ TR cells or alter levels of CD25 mRNA expression in treatment recipients. Taken together, these findings have far-reaching implications for the interpretation of all previous studies forming conclusions about CD4+CD25+ TR cell depletion in vivo.


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