IL-12 enhances CTL synapse formation and induces self-reactivity.
Immunological synapse formation between T cells and target cells can affect the functional outcome of TCR ligation by a given MHC-peptide complex. Although synapse formation is usually induced by TCR signaling, it is not clear whether other factors can affect the efficiency of synapse formation. Here, we tested whether cytokines could influence synapse formation between murine CTLs and target cells. We found that IL-12 enhanced synapse formation, whereas TGFbeta decreased synapse formation. The enhanced synapse formation induced by IL-12 appeared to be functional, given that IL-12-treated cells could respond to weak peptides, including self-peptides, to which the T cells were normally unresponsive. These responses correlated with expression of functionally higher avidity LFA-1 on IL-12-treated CTLs. These findings have implications for the function of IL-12 in T cell-mediated autoimmunity.
Markiewicz
Mary A
MA
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Wise
Erica L
EL
Buchwald
Zachary S
ZS
Cheney
Elizabeth E
EE
Hansen
Ted H
TH
Suri
Anish
A
Cemerski
Saso
S
Allen
Paul M
PM
Shaw
Andrey S
AS
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D054992:Immunological Synapses / Q000378:metabolism*; D018836:Inflammation Mediators / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*
D001324:Autoantigens; D018836:Inflammation Mediators; D018664:Interleukin-12