Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1993-8-26
pubmed:abstractText
Delayed-type hypersensitivity and allograft rejection are dependent upon the generation of Ag-specific T cell immune responses. The mixed lymphocyte reaction is a model of alloantigen-driven immunity and has provided significant insight into the mechanisms of T cell proliferation. Recently, soluble mediators, including TNF-alpha have been shown to be involved in the full expression of this response. In order to elucidate the potential mechanisms of cellular recruitment in the context of either delayed-type hypersensitivity or allograft rejection, we employed a mixed lymphocyte reaction to study the production of chemokines, monocyte chemoattractant protein-1 (MCP-1), and IL-8. Time-course experiments demonstrated that significant levels of MCP-1 and IL-8 were produced in allogeneic cultures as early as day 1, and that this relationship persisted over 6 days in culture. Northern blot analysis of chemokine mRNA confirmed the early induction of these genes in the allogeneic response. The levels of MCP-1 and IL-8 protein from mixed lymphocyte reaction supernatants as measured by specific ELISA were positively correlated with the proliferative response as measured by [3H]TdR uptake. Although significant MCP-1 and IL-8 were produced during a mixed lymphocyte reaction, these molecules did not participate in the proliferative response, as neutralizing antibodies to either MCP-1 or IL-8 had no effect on proliferation. In order to ascertain the mechanism for the induction of MCP-1 and IL-8 during the mixed lymphocyte reaction, experiments were performed in the presence of neutralizing anti-human TNF antibodies. Neutralization of TNF resulted in significant abrogation of MCP-1 and IL-8 production (75 +/- 5 and 87 +/- 2 percent, respectively). Cells isolated from the mixed lymphocyte reaction at day 6, demonstrated that MCP-1 and IL-8 Ag were localized to mononuclear phagocytes. These results demonstrate that potent chemokines, MCP-1 and IL-8, are produced during the evolution of a mixed lymphocyte reaction, and their induction is TNF-dependent.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
151
pubmed:geneSymbol
IL-8, MCP-1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1205-13
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Characterization of the production of monocyte chemoattractant protein-1 and IL-8 in an allogeneic immune response.
pubmed:affiliation
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't