Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-1-6
pubmed:abstractText
In this study, we suggest that CD8 levels on T cells are not static, but can change and, as a result, modulate CD8(+) T cell responses. We describe three models of CD8 modulation using novel weak-agonist (K1A) and super-agonist (C2A) altered peptide ligands of the HY smcy peptide. First, we used peripheral nonresponsive CD8(low) T cells produced after peripheral HY-D(b) MHC class I tetramer stimulation of female HY TCR transgenic and wild-type mice. Second, we used genetically lowered CD8(int) T cells from heterozygote CD8(+/0) mice. Finally, we used pre-existing nonresponsive CD8(low) T cells from male HY TCR transgenic mice. In CD8(low) and CD8(high) mice, presence of a lower level of CD8 greatly decreased the avidity of the peptide-MHC for HY TCR as reflected by avidity (K(D)) and dissociation constant (T(1/2)) measurements. All three models demonstrated that lowering CD8 levels resulted in the requirement for a higher avidity peptide-MHC interaction with the TCR to respond equivalently to unmanipulated CD8(high) T cells of the same specificity. Additionally, direct injections of wild-type HY-D(b) and C2A-D(b) tetramers into female HY TCR or female B6 mice induced a high frequency of peripheral nonresponsive CD8(low) T cells, yet C2A-D(b) was superior in inducing a primed CD8(+)CD44(+) memory population. The ability to dynamically modulate the size and responsiveness of an Ag-specific T cell pool by "CD8 tuning" of the T cell during the early phases of an immune response has important implications for the balance of responsiveness, memory, and tolerance.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
174
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
619-27
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15634879-Animals, pubmed-meshheading:15634879-Antigens, CD8, pubmed-meshheading:15634879-CD8-Positive T-Lymphocytes, pubmed-meshheading:15634879-Cell Differentiation, pubmed-meshheading:15634879-Cytotoxicity, Immunologic, pubmed-meshheading:15634879-Down-Regulation, pubmed-meshheading:15634879-Epitopes, T-Lymphocyte, pubmed-meshheading:15634879-Female, pubmed-meshheading:15634879-H-Y Antigen, pubmed-meshheading:15634879-Ligands, pubmed-meshheading:15634879-Lymphocyte Activation, pubmed-meshheading:15634879-Male, pubmed-meshheading:15634879-Mice, pubmed-meshheading:15634879-Mice, Inbred C57BL, pubmed-meshheading:15634879-Mice, Transgenic, pubmed-meshheading:15634879-Peptides, pubmed-meshheading:15634879-Protein Binding, pubmed-meshheading:15634879-Receptors, Antigen, T-Cell, pubmed-meshheading:15634879-Sex Characteristics, pubmed-meshheading:15634879-T-Lymphocyte Subsets, pubmed-meshheading:15634879-Transplantation Tolerance
pubmed:year
2005
pubmed:articleTitle
Peripheral "CD8 tuning" dynamically modulates the size and responsiveness of an antigen-specific T cell pool in vivo.
pubmed:affiliation
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599, USA. robmaile@bellsouth.net
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't