About: The majority of infiltrating CD8 T lymphocytes in multiple sclerosis lesions is insensitive to enhanced PD‐L1 levels on CNS cells

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About: The majority of infiltrating CD8 T lymphocytes in multiple sclerosis lesions is insensitive to enhanced PD‐L1 levels on CNS cells Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The majority of infiltrating CD8 T lymphocytes in multiple sclerosis lesions is insensitive to enhanced PD‐L1 levels on CNS cells
Creator	Arbour, Nathalie Newcombe, Jia Antel, Jack Pittet, Camille
Source	Medline; PMC
abstract	Central nervous system (CNS) cells locally modulate immune responses using numerous molecules that are not fully elucidated. Engagement of programmed death‐1 (PD‐1), expressed on activated T cells, by its ligands (PD‐L1 or PD‐L2) suppresses T‐cell responses. Enhanced CNS PD‐1 and PD‐L1 expression has been documented in inflammatory murine models; however, human CNS data are still incomplete. We determined that human primary cultures of astrocytes, microglia, oligodendrocytes, or neurons expressed low or undetectable PD‐L1 under basal conditions, but inflammatory cytokines significantly induced such expression, especially on astrocytes and microglia. Blocking PD‐L1 expression in astrocytes using specific siRNA led to significantly increased CD8 T‐cell responses (proliferation, cytokines, lytic enzyme). Thus, our results establish that inflamed human glial cells can express sufficient and functional PD‐L1 to inhibit CD8 T cell responses. Extensive immunohistochemical analysis of postmortem brain tissues demonstrated a significantly greater PD‐L1 expression in multiple sclerosis (MS) lesions compared with control tissues, which colocalized with astrocyte or microglia/macrophage cell markers. However, more than half of infiltrating CD8 T lymphocytes in MS lesions did not express PD‐1, the cognate receptor. Thus, our results demonstrate that inflamed human CNS cells such as in MS lesions express significantly elevated PD‐L1, providing a means to reduce CD8 T cell responses, but most of these infiltrating immune cells are devoid of PD‐1 and thus insensitive to PD‐L1/L2. Strategies aimed at inducing PD‐1 on deleterious activated human CD8 T cells that are devoid of this receptor could provide therapeutic benefits since PD‐L1 is already increased in the target organ. © 2011 Wiley‐Liss, Inc.
has issue date	2011-02-28(xsd:dateTime)
bibo:doi	10.1002/glia.21158
bibo:pmid	21360758
has license	no-cc
sha1sum (hex)	4bfec743cd9b5985470763fdbb807a2b00ff63ba
schema:url	https://doi.org/10.1002/glia.21158
resource representing a document's title	The majority of infiltrating CD8 T lymphocytes in multiple sclerosis lesions is insensitive to enhanced PD‐L1 levels on CNS cells
has PubMed Central identifier	PMC7165507
has PubMed identifier	21360758
schema:publication	Glia
resource representing a document's body	covid:4bfec743cd9b5985470763fdbb807a2b00ff63ba#body_text
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