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2017 ; 8
(ä): 987
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Distinctive Surface Glycosylation Patterns Associated With Mouse and Human CD4(+)
Regulatory T Cells and Their Suppressive Function
#MMPMID28871258
Cabral J
; Hanley SA
; Gerlach JQ
; O'Leary N
; Cunningham S
; Ritter T
; Ceredig R
; Joshi L
; Griffin MD
Front Immunol
2017[]; 8
(ä): 987
PMID28871258
show ga
Regulatory T-cells (Treg) are essential for maintaining immune homeostasis and
tolerance. Surface glycosylation is ubiquitous on mammalian cells and regulates
diverse biological processes. While it is currently well accepted that surface
glycan expression influences multiple aspects of T-cell function, little is known
about the relevance of glycosylation to Treg biology. This study aimed to profile
the surface glycosylation characteristics of Treg in various lymphoid
compartments of mouse and in human peripheral blood with comparison to
non-regulatory, conventional CD4(+) T-cells (Tconv). It also sought to determine
the relationship between the surface glycosylation characteristics and
suppressive potency of Treg. Lectin-based flow cytometric profiling demonstrated
that Treg surface glycosylation differs significantly from that of Tconv in the
resting state and is further modified by activation stimuli. In mouse, the
surface glycosylation profiles of FoxP3(+) Treg from spleen and lymph nodes were
closely comparable but greater variability was observed for Treg in thymus, bone
marrow, and blood. Surface levels of tri/tetra-antennary N-glycans correlated
with expression of proteins known to be involved in Treg suppressive functions,
including GITR, PD-1, PD-L1, CD73, CTLA-4, and ICOS. In coculture experiments
involving purified Treg subpopulations and CD4(+) or CD8(+) Tconv, higher surface
tri/tetra-antennary N-glycans was associated with greater Treg suppressive
potency. Enzymatic manipulation of mouse Treg surface glycosylation resulting in
a temporary reduction of surface N-glycans significantly reduced Treg capacity to
suppress Tconv activation through contact-dependent mechanisms. Overall, these
findings demonstrate that Treg have distinctive surface glycan characteristics
that show variability across anatomical locations and are modulated by activation
events. They also provide evidence of an important role for surface glycosylation
in determining Treg phenotype and suppressive potency. These insights may prove
relevant to the analysis of Treg in disease settings and to the further
development of Treg-based immunotherapies.