Analysis of allelic expression patterns of IL‐2, IL‐3, IL‐4, and IL‐13 in human CD4⁺ T cell clones

Abstract

The occurrence of monoallelic expression of cytokine genes in single cells has been convincingly demonstrated, but there have been few reports of this phenomenon in T cell clones. Here we describe studies on the expression of alleles of the human genes encoding IL-2, IL-3, IL-4, and IL-13 in human CD4 + T cell clones. In contrast to the results reported in mouse T cell clones and single human T cells, we found no evidence for the monoallelic expression of the IL-2, IL-3, and IL-13 genes. The gene for IL-4 showed an imbalance in expression from each allele, indicating differential expression of IL-4 alleles within or between IL-4-expressing cells.

Compensatory T-Cell Regulation in Unaffected Relatives of SLE Patients, and Opposite IL-2/CD25-Mediated Effects Suggested by Coreferentiality Modeling

“…Our unaffected-relatives IL2 model ascribes negative functional effects to the respective minor alleles of both rs11575812 and rs2069763 , but no effect to that of rs2069762 . In the context of the interpretation of all three minor alleles as independent haplotypes, this is consistent with the previously described relatively positive effect of rs2069762 G. These haplotype structures may have particular functional relevance since IL-2 is monoallelically expressed in single human T-cells [59], although not stably in expanded clones [60]. IL2 is also since long suspected for association with various disease phenotypes, but it has to be taken into account that linkage in the IL2 locus (including the discussed haplotype structure) extends to the neighboring IL21 gene and therefore association does not necessarily reflect IL-2-mediated effects.…”

STAT6 tunes maximum T cell IL‐4 production from stochastically regulated Il4 alleles

“…Il4 is not the only cytokine reported to have each allele regulated independently, although it is perhaps the most consistently reported as so (e.g. Bayley et al 12 ). Initial reports demonstrated IL-2 as monoallelically regulated, based among other findings on hemizygous and homozygous reporter mice to exhibit ≈2-fold abundance differentials in frequencies of cells transcribing from the locus, 33 similar to our general observations with the KN2 and G4 hemizygotes.…”

“…The independent regulation was hypothesized following the observation of the biased transcription of single Il4 alleles in long-term Th2 clones, 2,3,6,10,11 with 4-to > 32-fold differentials in transcription of one allele over the other in different Th2 cell lines. [10][11][12][13] Mariani et al 5 also elegantly demonstrated that accessibility of the Il4 locus in IL-4 producers was not a linked phenomenon and that allelic competence and expression were distinctly regulated events.…”

X-Chromosome Inactivation and Autosomal Random Monoallelic Expression as “Faux Amis”

“…In T cells, IL-2 was reported to be monoallelically expressed in T cells ( Hollander et al, 1998 ), whereas for IL-4 the expression was described as biallelic or monoallelic, depending on the clone ( Bix and Locksley, 1998 ) or the strength of the signal delivered through the TCR ( Rivière et al, 1998 ). Four subsequent studies on IL-2 reached different conclusions: whereas IL-2 was found to be biallelically expressed in human T cell clones ( Chiodetti et al, 2000 ; Bayley et al, 2003 ), in mice heterozygous for an IL-2-GFP transgene ( Naramura et al, 1998 ) and in single-cell RT-PCR experiments ( Rhoades et al, 2000 ), most cells expressed both IL-2 alleles but there were also single expressors. Overall, the data for IL-2 seem consistent with the data for IL-4 : under optimal and continuous stimulation, cells will tend to express both alleles, but at suboptimal levels of expression, there may be cells expressing only one of the alleles.…”