Hello,
I always had the assumption that innate-like T-cells (Gamma/Delta, NKT, MAIT) are less proliferative than conventionnal T-cells after activation. But actually, I do not find any papers to confirm or disprove this idea...
Does anybody can tell me more about it ?
Thanks !
Rémy
Hi Rémy,
It was thought that MAIT cells were hypoproliferative (Dusseaux et al. Blood. (2011) 117(4):1250-9). However, the publication of Kurioka et al. Mucosal Immunology (2015) 8, 429–440; doi:10.1038/mi.2014.81 showed that MAIT cells proliferate readily in response to E.coli, and that they show similar proliferative responses to conventional T cells after activation with anti-CD3/28/2 beads.
Hope this helps!
Jo
Innate T cells (which for me would not include gdT cells, but only the T cells selected by non-polymorphic MHC homologs) are natural memory phenotype T cells. I am not aware of any claim that memory T cells would be less responsive than naïve T cells, so likewise I would expect that innate T cells behave like memory T cells in regard to proliferation as well.
For MAIT/mNKT cells the Dusseaux paper Joannah mentioned shows - to my understanding - that mNKT cells are non-cycling under resting state conditions, but do so after activation (s.a. Le Bourhis Nat Imm 10).
Likewise for iNKT cells: under resting state conditions peripheral iNKT cells hardly proliferate (only ca. 5% of cells in the thymus are Ki67+ (Berzins Eur J Imm 2005) - similar the Ki67+ values for human (PBMCs) and mouse (e.g. spleen) iNKT cells are very low in my hands). The exceptions are recent thymic emigrant iNKT cells (Milpied Blood 2011) and NKT10 cells (Sag J Clin Invest 2014).
But following antigenic activation or during homeostatic proliferation (e.g. RAG-KOs) they strongly expand (e.g. Matsuda Nat Imm 2002). To be honest, I’m not aware of a publication looking for proliferation following innate activation (e.g. LPS) stimulation of iNKT cells.
So, I would say that innate T cells proliferate in a similar fashion after activation than other memory T cells.
For Vg2Vd2 T cells, the proliferation is triggered by the stimulus (HMBPP/IPP or Zol +IL-2), which is quite different from CD3/CD28+IL-2 for convention T cells. On our hand, we have always found that fresh PBMC cultures would be dominated by Vg2Vd2 T cells in the presence of HMBPP+IL-2 for 7-14 days, or dominated by ab T cells in the presence of CD3/CD28+IL-2.
And, Gerhard Wingender is right as at the least the expanded Vg2Vd2 T cells exhibited central memory or effector memory phenotype, rather than naive or EMRA. At this point, Vg2Vd2 T cells have some unique proliferation profiles.
However, the CD3-TCR complex of ab and gd T cells also has some differences as only a unique anti-CD3 clone can activate fresh Vg2Vd2 T cells. (10.1016/j.celrep.2014.04.049) Indeed, we also verify this in our bsAb constructs. This highlighted that the in vivo expansion was differently regulated for these two T cell subsets.
Besides, Vg2Vd2 T cells could expand more quickly than conventional T cells in vivo, as indicated in 10.1038/s41586-019-1817-8 (see the i.v. group in Fig.1 as well as the sourcedata1).
Therefore, one could negatively purify these cells, provide a signal 1/2/3 for optimal T cell activation/proliferation, to solve this question in vitro, while in vivo study showed that a more quickly expansion profile for innate T cells.