The findings in two clusters that are relevant for lymphocytes (cluster 4 in the web supplement) and B-lymphocytes (cluster 16, Figure 3) are further examples of type (i) predictions.
The DTIC treated subclones were lysed by in vivo-primed, in vitro-restimulated (with the relevant subclone) lymphocytes.
CD99 is involved in monocyte, neutrophil granulocyte and lymphocyte diapedesis [ 111- 113], but CD99L2 is not relevant for lymphocyte diapedesis to inflamed tissue [ 112].
Because of this strong and diagnostically relevant association, B lymphocytes were long suspected to be the main culprits in RA pathogenesis [ 1, 8].
This is particularly relevant for T lymphocytes as involution of the thymus essentially abrogates regeneration of T cells in middle age.
A 15-minute digestion at room temperature with this type of collagenase did not affect the ability to detect relevant antigens on lymphocytes by flow-cytometry (B220, CD3, CD4, CD11c, CD23, CD21, CD45) (data not shown).
Finally, we investigated the expression of candidate genes and the association of candidate variants in different populations, and examined IRGM expression in a physiologically relevant primary tissue (lymphocytes) from CD patients of known risk genotypes.
The addition of 50 μ M pyocyanin, a concentration that has been measured in the sputum of patients (36) and, thus, is pathophysiologically relevant, to Jurkat lymphocytes or neutrophils resulted in an immediate increase in superoxide anion production at the level of the mitochondria (Fig. 2A, B).
To determine whether this was relevant to DC lymphocytes we co-labelled 53BP1 and the shelterin protein TRF1 and used confocal microscopy to determine the extent of co-localization in DNA damage complexes known as telomere dysfunction-induced foci (TIFs) (Takai et al, 2003).
AID was initially thought to be only relevant in B-lymphocytes, where it is essential for somatic hypermutation and class-switch recombination [ 26, 27].
