Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-4-14
pubmed:abstractText
Efalizumab (anti-CD11a) interferes with LFA-1/ICAM-1 binding and inhibits several key steps in psoriasis pathogenesis. This study characterizes the effects of efalizumab on T-cell activation responses and expression of surface markers on human circulating psoriatic T cells during a therapeutic trial. Our data suggest that efalizumab may induce a unique type of T-cell hyporesponsiveness, directly induced by LFA-1 binding, which is distinct from conventional anergy described in animal models. Direct activation of T cells through different activating receptors (CD2, CD3, CD3/28) is reduced, despite T cells being fully viable. This hyporesponsiveness was spontaneously reversible after withdrawal of the drug, and by IL-2 in vitro. In contrast to the state of anergy, Ca(+2) release is intact during efalizumab binding. Furthermore, lymphocyte function-associated antigen-1 (LFA-1) blockade resulted in an unexpected downregulation of a broad range of surface molecules, including the T-cell receptor complex, co-stimulatory molecules, and integrins unrelated to LFA-1, both in the peripheral circulation and in diseased skin tissue. These observations provide evidence for the mechanism of action of efalizumab. The nature of this T-cell hyporesponsiveness suggests that T-cell responses may be reduced during efalizumab therapy, but are reversible after ceasing efalizumab treatment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD11a, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD2, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD8, http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha4beta1, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2, http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Function-Associated..., http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell, http://linkedlifedata.com/resource/pubmed/chemical/efalizumab
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1523-1747
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1182-91
pubmed:meshHeading
pubmed-meshheading:18239614-Adult, pubmed-meshheading:18239614-Aged, pubmed-meshheading:18239614-Antibodies, Monoclonal, pubmed-meshheading:18239614-Antigens, CD11a, pubmed-meshheading:18239614-Antigens, CD2, pubmed-meshheading:18239614-Antigens, CD28, pubmed-meshheading:18239614-Antigens, CD3, pubmed-meshheading:18239614-Antigens, CD4, pubmed-meshheading:18239614-Antigens, CD8, pubmed-meshheading:18239614-Down-Regulation, pubmed-meshheading:18239614-Female, pubmed-meshheading:18239614-Humans, pubmed-meshheading:18239614-Integrin alpha4beta1, pubmed-meshheading:18239614-Interleukin-2, pubmed-meshheading:18239614-Lymphocyte Activation, pubmed-meshheading:18239614-Lymphocyte Function-Associated Antigen-1, pubmed-meshheading:18239614-Male, pubmed-meshheading:18239614-Middle Aged, pubmed-meshheading:18239614-Psoriasis, pubmed-meshheading:18239614-Receptors, Antigen, T-Cell, pubmed-meshheading:18239614-T-Lymphocytes
pubmed:year
2008
pubmed:articleTitle
Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T-cell hyporesponsiveness.
pubmed:affiliation
Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 10065, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, N.I.H., Extramural