Research: More evidence to suggest that Dacluzimab does ot work via T cells

R
Perry JS, Han S, Xu Q, Herman ML, Kennedy LB, Csako G, Bielekova B.Inhibition of LTi Cell Development by CD25 Blockade Is Associated with Decreased Intrathecal Inflammation in Multiple Sclerosis. Sci Transl Med. 2012;4:145ra106.

Genetic polymorphisms  (Genetic variants) in the interleukin-2 receptor α (IL-2Rα) chain
(CD25) locus are associated with several human autoimmune diseases,
including multiple sclerosis
(MS). Blockade of CD25 by the humanized monoclonal antibody daclizumab
decreases MS-associated inflammation but has surprisingly limited direct
inhibitory effects on activated T cells.

The present study describes
unexpected effects of daclizumab therapy on innate lymphoid cells
(ILCs). The number of circulating retinoic acid receptor-related orphan
receptor γt-positive ILCs, which include lymphoid tissue inducer (LTi)
cells, was found to be elevated in untreated MS patients compared to
healthy subjects. Daclizumab therapy not only decreased numbers of ILCs
but also modified their phenotype away from LTi cells and toward a natural killer (NK) cell lineage.

Mechanistic studies indicated that
daclizumab inhibited differentiation of LTi cells from CD34(+)
hematopoietic progenitor cells (stem cells) , steering
their differentiation toward immunoregulatory CD56(bright) NK cells
through enhanced intermediate-affinity IL-2 signaling. Because adult LTi
cells may retain lymphoid tissue-inducing capacity or stimulate
adaptive immune responses, we indirectly measured intrathecal
inflammation in daclizumab-treated MS patients by quantifying the
cerebrospinal fluid chemokine (C-X-C motif) ligand 13 and immunoglobulin
G index. Both of these inflammatory biomarkers were inhibited by
daclizumab treatment. Our study indicates that ILCs are involved in the
regulation of adaptive immune responses, and their role in human
autoimmunity should be investigated further, including their potential
as therapeutic targets.

This yet more evidence that the T cell inhibitor drug, do not appear to work via T cells but stimulate natural killer cells.

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