Linked Life Data

8168105

Source:http://linkedlifedata.com/resource/pubmed/id/8168105

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1994-6-2
pubmed:abstractText
Lymph nodes draining a progressively growing tumor contain T-cells which can be activated sequentially by anti-CD3 and IL-2 to differentiate into tumor-specific effector cells. In this study, long-term cultured T-cell lines were established from activated MCA 106 tumor-draining lymph node cells by periodic stimulation with irradiated tumor cells in the presence of low concentrations of IL-2 (< or = 60 International units/ml). Such long-term cultured cell lines maintained therapeutic effects when transferred to tumor-bearing mice. Although the initial anti-CD3/IL-2-activated T-cells displayed a broad distribution of T-cell antigen receptor beta chain variable region (V beta) usages, long-term cultured cells were dominated by T-cells expressing a few V beta elements. Of six cell lines, only three V beta phenotypes (V beta 5, 11, 13) were identified, and individual cell lines frequently expressed a single V beta gene product. Despite restricted V beta expression, each cell line mediated tumor-specific reactivity in adoptive immunotherapy. Many T-cell clones were isolated from long-term cell lines. Three V beta 13 T-cell clones demonstrated specific in vivo antitumor effects, whereas two V beta 11 and two V beta 5 clones revealed a significant degree of cross-reactivity against the antigenically distinct MCA 205 tumor. Although the initial anti-CD3/IL-2-activated cells lacked demonstrable cytotoxic reactivity, T-cell clones derived from them exhibited cytotoxic effects to the MCA 106 tumor cells. The specificity of the cytotoxicity mediated by each clone reflected its in vivo antitumor effects. Furthermore, studies of in vivo localization of cloned T-cells demonstrated tumor-specific infiltration of the 5A2 (V beta 13) clone to the MCA 106 tumor metastases, whereas clone 9H6 (V beta 5) revealed some accumulation in the MCA 205 tumor. Again, the in vivo antitumor effects of the 9H6 clone correlated with its in vivo infiltration into the specific MCA 106 and the nonspecific MCA 205 metastases. Taken together, the long-term culture of anti-CD3/IL-2-activated tumor-draining lymph node cells resulted in selective expansion of a few T-cells as evidenced by the limited T-cell receptor V beta expression. Our results also demonstrated that systemically administered antitumor T-cell clones gained access and accumulated at metastatic tumor sites, and the degree of infiltration correlated with the specificity of the in vivo antitumor effect as well as the in vitro cytotoxic activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2744-50
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Characteristics and in vivo homing of long-term T-cell lines and clones derived from tumor-draining lymph nodes.
pubmed:affiliation
Department of Surgery, University of Michigan, Ann Arbor 48109.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.