Table 1.

Activation-induced CD4 T-cell cytokines and corresponding receptors on LinIEL lines

GeneFCpfpMSReceptor genesP1P2P3
IL2119.20.000xIL21R/IL2RGxxx
IL315.60.000xIL3RA/CSF2RB
XCL117.90.000XCR1
CCL115.60.000xCCR8
IL1313.40.000xIL4R/IL13RA1
CSF29.60.000xCSF2RA/CSF2RB
IL89.40.000xIL8RA/IL8RB
CCL49.10.000CCR5
IL27.60.000xIL2RA/IL2RB/IL2RGxxx
CCL4L17.50.000xCCR5
TNF6.60.000xTNFRSF1Axxx
TNFRSF1Bxxx
CCL205.10.001CCR6xxx
CCL3L15.50.001xCCR5/CCBP2
IL226.40.001xIL10RA/IL22RA1
AREG5.10.002xEGFR
PDGFA4.90.002PDGFRA/PDGFRB
IL106.30.003xIL10RA/IL10RBxxx
IL1A4.30.003IL1R1/IL1RAP
IL1R2/IL1RAP
HBEGF4.00.003xEGFR
XCL23.90.004XCR1
IFNG4.10.004xIFNGR1/IFNGR2x
CD40LG3.80.005xTNFRSF5
LTA3.70.006TNFRSF1Axxx
TNFRSF1Bxxx
TNFRSF14xxx
FASLG3.70.007TNFRSF6xx
CCL33.90.006xCCR5/CCBP2
IL54.50.007IL5RA/CSF2RB
CSF13.50.011xCSF1R
NAMPT3.30.012None
F53.80.015None
IGF22.90.042IGF1R
IGF2Rxxx
LIF2.40.047xLIFR/IL6ST
  • Gluten-specific CD4+ T-cell clone L10 was activated using plate-bound CD3/CD28 or control antibodies, and RNA isolated at 3 h after activation was analyzed using an Affymetrix human ST1.0 array (GEO accession no. GSE73599). The experiment was performed in triplicate and yielded a list of 141 genes significantly induced by CD3/CD28 cross-linking. Of these, 31 transcripts encoding secreted proteins are listed, with fold change (FC) and percentage of false-positive predictions. RT-qPCR experiments confirmed the induction of IL10, IL13, IL21, IL22, IFNG, LIF, and AREG transcription in L10 and four additional gluten-specific CD4+ T-cell clones, both on CD3/CD28 cross-linking and on recognition of cognate peptide (data not shown). Supernatants from this clone were analyzed by MS at 4 h after activation in serum-free medium. Three independent biological replicates were performed, and proteins (encoded by the genes in the first column) detected in supernatants from the CD3/CD28-activated T-cell clone are marked with an x. The corresponding receptor genes are listed, and the presence of their transcripts in three LinIEL lines from RCDII patients, previously determined using an Illumina array (3) (GEO accession no. GSE33078), is indicated. IL21, IL2, TNF, and IL10, shown in bold type, are the only cytokines for which activation detectably induced their transcription and secretion and for which the malignant LinIEL lines express a receptor.