Linked Life Data

1531321

Source:http://linkedlifedata.com/resource/pubmed/id/1531321

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1992-3-18
pubmed:abstractText
Previous studies have demonstrated that progressive growth of the weakly immunogenic MCA 106 murine sarcoma stimulated, in the draining lymph nodes, the production of tumor-sensitized but not fully functional preeffector lymphocytes. These lymphocytes could develop into specific immune effector cells after sequential in vitro activation with anti-CD3 monoclonal antibody and interleukin 2 (IL-2). In this study, we analyzed cellular requirements for in vivo sensitization of preeffector cells, for generation of immune effector cells by the method of anti-CD3/IL-2 activation, and for adoptive immunotherapy mediated by activated cells. By selective depletion of T-cell subsets in vivo, we found that tumor regression after systemic adoptive immunotherapy required the collaboration of activated CD4+ and CD8+ cells. It was further demonstrated that CD8+ immune cells alone could mediate antitumor effects if exogenous IL-2 was provided in vivo. These results suggest that CD8+ cells served as immediate effector cells, whereas CD4+ immune cells provided a helper function via the secretion of IL-2. During in vitro anti-CD3/IL-2 activation, generation of effector cells depended on the collaborative interaction between previously sensitized CD4+ and CD8+ preeffector cells. At the stage of in vitro activation, the addition of IL-2 could not substitute the function of CD4+ cells. We next examined whether the sensitization of preeffector cells in the draining lymph nodes required cellular interactions between CD4+ and CD8+ T-cells. By in vivo depletion of T-cell subsets during tumor growth, we found that CD4+ cells were sensitized independently of CD8+ cells. More interestingly, in vivo sensitization of CD8+ preeffector cells also occurred independently in the absence of a CD4+ helper cell response. The lack of T-cell-T-cell interactions in vivo may explain the failure of effector cell generation during progressive tumor growth. Taken together, these results demonstrate that the anti-CD3/IL-2 activation defines an immune response distinct from many previously described mechanisms of antitumor immune responses.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1129-36
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Cellular interactions in effector cell generation and tumor regression mediated by anti-CD3/interleukin 2-activated tumor-draining lymph node cells.
pubmed:affiliation
Department of Surgery, University of Michigan, Ann Arbor 48109.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't