Self-renewal of T-cells and chemoresistance

by Alexey Bersenev on November 27, 2009 · 2 comments

in Journal club

As you know the fundamental quality of stem cells is self-renewal. Ability to self-renew and differentiate to mature cell types underlies the phenomenon of symmetrical and asymmetrical stem cell division. But not only stem cell can self-renew. It was shown that some subsets of T-lymphocytes (T-cells) can self-renew and divide asymmetrically. But what is biological role of this phenomenon in T-cells? Why do non-stem cells need to self-renew? Can they do it without specific niche?

2 recent studies indicate that self-renewing T-cells form immunological memory in mouse and human. What interests me are the remarkable similarities between self-renewing T-cells and hematopoietic stem cells (HSCs) despite their differing biological functions:

    – Stem-cell like CD8+ memory T-cells express HSC markers: c-Kit+, Rh123-, Sca1+, CD122+;
    – self-renewal could be regulated by pathways in common with those in HSC, such as Wnt;
    – they are quiescent;
    – expressing ABC-superfamily multidrug efflux proteins and chemoresistant.

Why is it significant and what can we learn from this?

    – When you start to search stem-cell-like populations you should apply all of “stemness” markers (surface phenotype, quiescence, metabolic activity, pathways…) and you will find them; It works for many tissues and for cancer(!);
    – Stem-cell-like memory CD8+ T-cells stimulated through Wnt-pathway could be effectively use therapeutically for so-called “adoptive immunotherapy” in cancer and infections;
    – Using Wnt-pathway priming we can theoretically make tumor-specific and antigen-specific T-cell based vaccines. These vaccines could induce long-term T-cell memory and efficiently target intracellular pathogens and cancer;
    – Because adult stem cells, cancer stem cells and self-renewing T-cells share common features (chemoresistance, quiescence…) chasing for efficient killing of the cancer we can also kill memory T-cells and shut down long-lasting immunity after therapy. Bad news.
    – The good news is that stem-cell-like memory T-cells successfully survive anti-cancer chemotherapy and provide immunity against infections after that.

I’d like to finish by quote from the commentary:

However, as the authors themselves state, a more conclusive demonstration of stem cell- like characteristics of this subset (such as serial adoptive transfers) will be required before a clear link to ‘‘memory stem cells’’ can be drawn; this will also require transmission of the findings to suit- able animal models, where more conclu- sive experiments can be performed. Regardless of these limitations, with the currently available data it is tempting to speculate that the CD161hiIL-18Rhi CD8+ memory T cell subset is not only a crucial subset for immune reconstitution during temporary lymphopenia but also a central player in the maintenance of CD8+ T cell memory in healthy individuals.

{ 2 comments… read them below or add one }

hope November 28, 2009 at 9:15 am

I surely agree with you, stem cells are the life givers of human body and their use in the right way will lead to many new discoveries in medical sciences.


Researcher December 5, 2009 at 3:05 am

Dear Alex,

May I ask you to attach a pdf of the “Can they do it without specific niche?” paper.

Many thanks.


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