3 years ago

CD4+CD28null T Cells Are Not Alloreactive Unless Stimulated by IL-15

W Verschoor, R Kraaijeveld, C. C Baan, N. H. R Litjens, M. G. H Betjes, B Dedeoglu, M Klepper
Proinflammatory, cytotoxic CD4+CD28null T cells can be substantially expanded in patients with end-stage renal disease. These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4+CD28null T cells were stimulated with HLA-mismatched antigen presenting cells in the absence/presence of exogenous cytokines. Alloreactive potential was evaluated by proliferation, degranulation, cytotoxicity and cytokine production. Furthermore, their suppressive capacity was assessed by measuring inhibition of proliferating alloreactive CD28+ T cells. CD4+CD28null T cells contained alloreactive (CD137+) T cells but did not proliferate in response to allogeneic stimulation, unless IL-15 was added. However, they could proliferate upon stimulation with CMV-antigen without exogenous cytokines. IL-15 increased the frequency of proliferating alloreactive CD4+CD28null T cells to 30.5% without inducing CD28 expression (p<0.05). After allogeneic stimulation together with IL-15 and IL-21, frequency of degranulating CD107a+CD4+CD28null T cells increased significantly from 0.6% to 5.8% (p<0.001). Granzyme B and perforin positivity remained similar, but production of IFN-γ and TNF-α increased by the combination of IL-15 and IL-21 (p<0.001 and p<0.05, respectively). Finally, CD4+CD28null T cells did not show significant suppression. Thus, CD4+CD28null T cells represent a population with absent alloreactivity unless IL-15 is present. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/ajt.14480

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.