PD-L2 Elbows out PD-L1 to Rescue T Cell Immunity to Malaria

Crompton, Peter D.; Pierce, Susan K.

doi:10.1016/j.immuni.2016.08.001

Cited by 7 publications

(6 citation statements)

References 9 publications

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“…Our data evaluating net T cell activation in the context of different concentrations of soluble PD‐1 pathway members evoke recent findings of Karunarathne et al 54 . That group showed that PD‐L1 and PD‐L2 have opposing actions upon T cell activation in a (mouse) model of malaria (see Ref 55 . for a review).…”

Section: Discussionsupporting

confidence: 84%

“…Our data evaluating net T cell activation in the context of different concentrations of soluble PD-1 pathway members evoke recent findings of Karunarathne et al 54 That group showed that PD-L1 and PD-L2 have opposing actions upon T cell activation in a (mouse) model of malaria (see Ref. 55 for a review). They showed that as expected, PD-L1:PD-1 interaction suppresses T cell activation, in that case rendering mice susceptible to malarial death.…”

Section: Discussionsupporting

confidence: 83%

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Expression and T cell regulatory action of the PD‐1 immune checkpoint in the ovary and fallopian tube

Johnson

Kim

Sam

et al. 2022

American J Rep Immunol

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Problem: Immune cell trafficking and surveillance within the ovary and fallopian tube are thought to impact fertility and also tumorigenesis in those organs. However, little is known of how native cells of the ovary and fallopian tube interact with resident immune cells. Interaction of the Programmed Cell Death Protein-1 (PD-1/PDCD-1/CD279) checkpoint with PD-L1 is associated with downregulated immune response.We have begun to address the question of whether PD-1 ligand or its receptors (PD-L1/-L2) can regulate immune cell function in these tissues of the female reproductive tract.Method of study: PD-1 and ligand protein expression was evaluated in human ovary and fallopian tube specimens, the latter of which included stages of tubal cell transformation and early tumorigenesis. Ovarian expression analysis included the determination of the proteins in human follicular fluid (HFF) specimens collected during in vitro fertilization procedures. Finally, checkpoint bioactivity of HFF was determined by treatment of separately-isolated human T cells and the measurement of interferon gamma (IFN𝛾).

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 83%

Expression and T cell regulatory action of the PD‐1 immune checkpoint in the ovary and fallopian tube

Johnson

Kim

Sam

et al. 2022

American J Rep Immunol

View full text Add to dashboard Cite

show abstract

“…Our data evaluating net T cell activation in the context of different concentrations of soluble PD-1 pathway members evoke recent findings of Karunarathne et al 52 . That group showed that PD-L1 and PD-L2 have opposing actions upon T cell activation in a (mouse) model of malaria (see 53 for a review). They showed that as expected, PD-L1:PD-1 interaction suppresses T cell activation, in that case rendering mice susceptible to malarial death.…”

Section: Discussionmentioning

confidence: 99%

Expression and T cell Regulatory Action of the PD-1 Immune Checkpoint in the Ovary and Fallopian Tube

Johnson

Sam

Asokan

et al. 2020

Preprint

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16The Programmed Cell Death Protein-1 (PD-1/PDCD-1/CD279) checkpoint has powerful immunomod-17 ulatory action, including in the context of cancer. PD-1 receptor activation by its ligands (PD-18 L1/2) is associated with downregulated immune response, and tumor cells can avoid surveillance 19 via PD-1 and/or ligand expression. While receptor expression is largely limited to lymphoid, 20 myeloid, and tumor cells, we show that membrane bound and soluble variants of PD-1 and lig-21 ands are also expressed by permanent constituent cell types of the human ovary and fallopian 22 tube, including granulosa cells and oocytes. PD-1 and soluble ligands were highly enriched in ex-23 osome fractions in human follicular fluid at bioactive levels that can control T cell PD-1 activation. 24 PD-1 checkpoint signaling may be involved in physiological ovarian functions including follicle, 25 and ultimately, germline and embryo immune-privilege. 26PD-1.28 54 cells [29][30][31][32][33][34][35] . Early transformation events can result in serous tubal intraepithelial lesions (STILs), 55 which are characterized by a "p53 signature" in morphologically unremarkable FTE cells, visi-56 ble on immunohistochemical staining as overexpression in 12 or more consecutive non-ciliated 57 cells. Mutations in the tumor suppressor can result in either nuclear stabilization of the mutant 58 p53 variant, or, in loss of p53 expression 36 . STILs can then progress to another stereotypical stage, 59 the serous tubal intraepithelial carcinoma (STIC) 30,37,38 . STIC cells detach from the tubal lumen 60 and engraft at distant sites within the peritoneum, including the surface of the ovary at ovulation 61 site(s) 39,40 . 62During a preliminary evaluation of Pd-1 pathway protein expression in immune cells within 63 the mouse ovary, we detected broad expression of the receptor and ligands in the organ, in both 64 somatic cells and oocytes. There was also an existing report in a publicly-available large-scale 65 gene expression screen (LifeMap Discovery R ) that showed that PD-1 pathway transcripts are de-66 tectable in human cumulus granulosa cells (HCGC). Because of potential relevance of these initial 67 data to ovarian function and ovarian cancer development, a more extensive analysis of the PD-1 68 checkpoint in the human ovary and fallopian tube was warranted. We tested whether the PD-1 69 checkpoint acts within the human ovary and fallopian tube in ways suggestive of physiological 70 function, including testing whether soluble PD-1 or ligand proteins are present in human follicular 71 fluid (HFF) at levels capable of regulating immune function. 72 Results 73In an immunohistochemical study of both pre-and postmenopausal human ovarian tissue ( Fig. 74 1), we found that PD-1, PD-L1, and PD-L2 are are widely expressed, and this was conserved in the 75 mouse ovary ( Fig. S1, human tonsil positive controls shown in Fig. S2). In human premenopausal 76 specimens (n=8 unique patient samples evaluated), PD-1 was detectable in the oocytes of non-77 growing (i...

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“…The ultimate outcome of T cell activation is determined by the balance of costimulatory and coinhibitory molecule signals received during T cell priming or recall (19). In addition to naive precursors, memory T cells are potently regulated by ligation of coinhibitory receptors on their cell surfaces (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%