Linked Life Data

8110726

Source:http://linkedlifedata.com/resource/pubmed/id/8110726

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-3-28
pubmed:abstractText
Treatment of lethally irradiated mice with a short course of high-dose interleukin (IL)-2 markedly inhibits acute and chronic graft-versus-host disease (GVHD), while preserving a graft-versus-leukemia (GVL) effect of allogeneic T-cells. We recently demonstrated that this GVL effect, observed with the EL4 leukemia/lymphoma in the A/J-->B10 strain combination, was mediated by CD8+ A/J T-cells in a CD4-independent fashion. IL-2 inhibited only the activity of CD4+ cells, and not that of CD4-independent CD8+ T-cells in A/J spleen cell inocula. This inhibition of CD4 function was sufficient to markedly inhibit GVHD, thus explaining the dissociation of GVHD and GVL in IL-2-treated mice. We have now performed studies to determine the capacity of IL-2 to inhibit GVHD induced across a variety of different histocompatibility barriers. IL-2 significantly delayed GVHD mortality in three of four additional fully major histocompatibility complex (MHC) plus minor-disparate strain combinations when CD4+ T-cells were given. Numbers of CD8+ T-cells comparable to those that might contaminate human marrow demonstrated a relatively poor capacity to produce acute GVHD when given without CD4+ cells in all of three additional strain combinations evaluated. In one of these strain combinations (B10-->BALB/c), IL-2 protected against acute but not chronic GVHD mortality when CD4+ cells were given with or without CD8+ cells. In one fully allogenic strain combination, B10-->A/J, IL-2 did not inhibit the GVHD produced by CD4+ cells given with or without CD8+ cells. IL-2 was unable to inhibit CD8-mediated GVHD in strain combinations differing at isolated class I MHC loci. In a strain combination differing only at multiple minor histocompatibility antigen (HA) loci, B10-->C3H.SW, GVHD was largely CD8-dependent, but IL-2 did not inhibit the small CD4-mediated component of GVHD. Together, these results suggest that IL-2 inhibits a restricted subset of CD4 cells or functions, and that the type of CD4 activities mediating GVHD is determined by the particular histoincompatibilities between donor and host.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1067-5582
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11-21
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Strain dependence of interleukin-2-induced graft-versus-host disease protection: evidence that interleukin-2 inhibits selected CD4 functions.
pubmed:affiliation
Transplantation Research Biology Center, Massachusetts General Hospital, Harvard Medical School, Boston 02129-2060.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't