T cell Activation and Regulation

Introduction

T cells residing in the airways are elementary for protection against airborne pathogens. This protection is superior relative to that provided by circulating T cells. While the mechanisms by which T cells are recruited to the lungs are increasingly appreciated, a major question remains how and where these cells persist for long after clearance of the initial infection. Other than circulating cells these cells do not receive pro-survival signals within lymphoid organs and other yet elusive tissue signals must ensure their survival. Finding new clues into tissue T cell biology under health and disease is essential to develop ways to induce protective mucosal immunity but may also find utility in treating autoimmunity and enhancing immunity to cancer

We have the following goals:

  • To identify composition of the lung T cell repertoire at the single cell level.
  • To enhance our fundamental understanding of the signals regulating T cells in the tissue.
  • To identify the role and antigen specificity of tissue T cells in the healthy lungs and lung cancer.

Highlights

We have characterized a novel population of lung CD8+ T cells and identified a role for the Notch signaling pathway in their maintenance (Hombrink et al., Nat Immunol 2016, NRC Handelsblad Oct. 29th 2016). Thereafter, I was supported by a Veni fellowship (NWO) to continue my work as a junior group leader.

In that period I developed novel research lines by performing single-cell RNA sequencing and imaging on T cells obtained from paired tumor, lung and blood samples. In addition I followed up on the role and characteristics of CD4+ T cells beyond healthy lung tissue and studied CD4+ T cells in the NSCLC tumor environment (Oja et al., Mucosal Immunol 2018).

My major finding in this period, on CD4+ TRM, was their exceptional capacity to produce pro-inflammatory cytokines in the tumor environment (Oja et al., Front Immunol 2018).

Medical needs

Cancer

Funding

  • PPOC and PPOR grants (internal funding in competition), together with Dr. J.van Buul and Dr. W. van Esch, Sanquin.
  • NWO VENI grant

 

Our research
Pleun (P.) Hombrink, PhD T cell activation and regulation
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