title: Cutting Edge: Anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells.
abstract: CD4+CD25+ T regulatory (T(R)) 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 T(R) cell supplementation and depletion. Contrary to dogma, we report here that injection of anti-CD25 mAb results in the functional inactivation, not depletion, of T(R) 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+ T(R) cells. In addition, anti-CD25 mAb treatment fails to both reduce the number of Thy1.1+ congenic CD4+CD25+ T(R) 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+ T(R) cell depletion in vivo.
authors.affiliation: Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Kohm
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: McMahon
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Podojil
authors.forename: Wendy Smith
authors.initials: WS
authors.lastname: Begolka
authors.forename: Mathew
authors.initials: M
authors.lastname: DeGutes
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Kasprowicz
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation; D007267:Injections; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2