Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. In a phase II clinical trial, high-dose immunosuppressive therapy combined with autologous CD34+ hematopoietic stem cell transplant resulted in 69.2% of subjects remaining disease-free without evidence of relapse, loss of neurological function or new MRI lesions through year 5 post-treatment. A combination of CyTOF mass cytometry and multi-parameter flow cytometry was used to explore the reconstitution kinetics of immune cell subsets in the periphery post HSCT and the impact of treatment on the phenotype of circulating T cells in this study population. Repopulation of immune cell subsets progressed similarly for all patients studied 2 years post therapy, regardless of clinical outcome. At month 2, monocytes and NK cells were proportionally more abundant, while CD4 T cells and B cells were reduced, relative to baseline. In contrast to the changes observed at earlier time points in the T cell compartment, B cells were proportionally more abundant and expansion in the proportion of naïve B cells was observed 1 and 2 years post therapy. Within the T cell compartment, the proportion of effector memory and late effector subsets of CD4 and CD8 T cells was increased, together with transient increases in proportions of CD45RA- Tregs, and Th1 cells, and a decrease in Th17.1 cells. While none of the treatment effects studied correlated with clinical outcome, patients that remained healthy throughout the 5-year study had significantly higher absolute numbers of memory CD4 and CD8 T cells in the periphery prior to stem cell transplantation
But it does tell us something about how immune populations reappear after depletion.
(1). It says that when you deplete T cells it is the memory cell population that expands up the quickest and indeed that is what was seen after treatment with alemtuzumab and also CD4 depleting antibody. It is laos seen in the animals.
(2). In contrast, B cell repopulation is seen with a a surge of immature that convert into naive/mature cells and this is seen following alemtuzumab and rituximab treatment and presumably ocrelizumab treat when the B cell subset reconstitution data in MS, is eventually shown.
Remember these two facts when I talk about this in the not too distant future.
This does not tell us if disease is going to re-activate and indeed is going to create the smoke screen, when we look for which cell types are going to trigger relapse.
There is a suggestion of increases in T regs (yeah), based on proportions, just like that reported after alemtuzumab and a decrease in Th17 so dogma can be preserved. We say this with the DMF study last week and when you look at absolute numbers you get a different answer,
Earlier this year we have pinned out mast on the memory B cell and one would hope that if you look at this population there may be some change to correlate with disease activity.
Free read the paper CLICK
However, the study only examined 23 pwMS and of them only 7/23 relapsed, so we are looking for a wood made up of a few twigs, so are we going to find the wood in a thicket?
However, in this study they did not even look for the right wood as they only reported examination of T memory cell function.
So the B memory cell idea is not dead….yet.
But it shows us where the science interest is, and that is Th17, T reg and T cells, T cells, T cells.
I’ll write to the authors so they can put me out of my misery with knowing what happens to B memory cells.
However, we know from rituximab studies that you can relapse and have no B cells in the blood so it is not a dead idea yet. Likewise if EBV is in the frame the memory cells will repopulate like crazy.
Importantly the main action may not be in the blood, but if new lesions are forming surely somethings happens.