Interleukin-15 expression in atherosclerotic plaques: an alternative pathway for T-cell activation in atherosclerosis?
T-cell activation in atherosclerotic plaques is thought to be initiated by plaque-derived antigens, such as oxidized LDL (oxLDL). An alternative pathway of T-cell activation independent of antigen stimulation, mediated by the cytokine interleukin (IL)-15, was recently described. We investigated IL-15 expression in atherosclerotic plaques in relation to plaque morphology, inflammatory cells, T-cell activation, and oxidation-specific epitopes by use of immunohistochemistry. In situ hybridization was used to evaluate IL-15 mRNA expression. We also studied the proliferative response of plaque-derived T-cell lines to IL-15 in vitro using [(3)H]thymidine incorporation. Fresh-frozen specimens were classified as fibrous (n=9), fibrolipid (n=8), and lipid-rich (n=14) plaques; normal vessels (n=4) served as reference. Expression of IL-15 mRNA and protein was found almost solely in fibrolipid and lipid-rich plaques, associated with oxLDL-positive macrophages. Sequential immunostains revealed colocalization between IL-15- and CD40L-positive T cells. Moreover, plaque-derived T-cell lines were highly responsive to IL-15. Hence, IL-15 could provide a pathway for antigen-independent T-cell activation.
Houtkamp
M A
MA
Department of Cardiovascular Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
van Der Wal
A C
AC
de Boer
O J
OJ
van Der Loos
C M
CM
de Boer
P A
PA
Moorman
A F
AF
Becker
A E
AE
D000368:Aged; D001158:Arteries / Q000276:immunology / Q000473:pathology; D001161:Arteriosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014158:Transcription, Genetic
D019409:Interleukin-15; D012333:RNA, Messenger