Invariant NKT Cells Biased for IL-5 Production Act as Crucial Regulators of Inflammation

Abstract

Although invariant NKT (iNKT) cells play a regulatory role in the pathogenesis of autoimmune diseases and allergy, an initial trigger for their regulatory responses remains elusive. In this study, we report that a proportion of human CD4+ iNKT cell clones produce enormous amounts of IL-5 and IL-13 when cocultured with CD1d+ APC in the presence of IL-2. Such IL-5 bias was never observed when we stimulated the same clones with α-galactosylceramide or anti-CD3 Ab. Suboptimal TCR stimulation by plate-bound anti-CD3 Ab was found to mimic the effect of CD1d+ APC, indicating the role of TCR signaling for selective induction of IL-5. Interestingly, DNA microarray analysis identified IL-5 and IL-13 as the most highly up-regulated genes, whereas other cytokines produced by iNKT cells, such as IL-4 and IL-10, were not significantly induced. Moreover, iNKT cells from BALB/c mice showed similar IL-5 responses after stimulation with IL-2 ex vivo or in vivo. The iNKT cell subset producing IL-5 and IL-13 could play a major role in the development of allergic disease or asthma and also in the immune regulation of Th1 inflammation.

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

“…49,50 A fraction of human NKT has also been shown to secrete high amounts of IL-5 and IL-13. 18,50,51 Therefore, secretion of these two cytokines by DP TAL suggest that these cells might play, at the effector level, roles similar to those of NKT. Nonetheless, DP and NKT likely have different ligands because DP do not express the NKT invariant TCR Va24 and in addition lack CD56.…”

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

“…Later studies revealed that while this robust IL-4 production was a signature of iNKT cells, it certainly was not the only cytokine iNKT cells can produce. To date, iNKT cells have been shown to produce IFN-γ and IL-4, as well as IL-2, IL-5, IL-6, IL-10, IL-13, IL-17, IL-21, TNF-α, TGF-β and GM-CSF ( Figure 1A) [21][22][23][24][25][26]. iNKT cells are also known to produce a vast array of chemokines [27].…”

Serum Interleukin-5 Changes in Partly Controlled Atopic Asthmatic Children

“…Allergic diseases, including asthma, are characterized by inflammation with pronounced infiltration of eosinophils and CD4+ T cells. IL-5 is a cytokine that is highly specific for eosinophilic inflammation and was originally found as 'T-cell replacing factor' that is secreted from T cells to stimulate antibody production from activated B cells [16]. IL-5 seems to be the primary cytokine involved in vivo in the production, differentiation, maturation and activation of eosinophils [9].…”