Double negative (DN) T cells are expanded in patients with autoimmune lymphoproliferative syndrome (ALPS), most likely due to a deficiency in fas-dependent apoptosis.
There is considerable controversy on the origin as well as function of these cells, but I'm wondering about another possibility: Could (at least part of them) actually be NKT cells?
DN T cells as defined by TCRαβ+(CD3+)CD4-CD8- were identified before NKT cells became well known. I found that clinical diagnosis of the percentage of these cells still relies on characterisation by these markers. They would however not exclude NKT cells. Is there a possibility that instead of DN T cells, it's actually the NKT cells which expand for some reason?
Dear Susanne
DN T cells in ALPS-FAS patients are not NKT cells. First, they have a variable TCRa repertoire. Second, they don't stain positive with aGalCer, and third, they mostly derived from CD8 preipheral mature T cells (Bristeau-Leprince et al JI 2008). They also highly express HLA-class II AND CD45RA. They are probably exhausted CD8 T cells waiting for a death trigger.
But, in patients presenting with ALPS without genetic eatiology (ALPS-U) it is not excluded that NKT cells can expand and thus be misleading if not carefully searched for.
All the best
Frédéric
Dear Susanne
DN T cells in ALPS-FAS patients are not NKT cells. First, they have a variable TCRa repertoire. Second, they don't stain positive with aGalCer, and third, they mostly derived from CD8 preipheral mature T cells (Bristeau-Leprince et al JI 2008). They also highly express HLA-class II AND CD45RA. They are probably exhausted CD8 T cells waiting for a death trigger.
But, in patients presenting with ALPS without genetic eatiology (ALPS-U) it is not excluded that NKT cells can expand and thus be misleading if not carefully searched for.
All the best
Frédéric
It would have been nice, as others have also wondered, but I concur with everything Frédéric says. In addition, Fas/Lpr mice also have expanded polyclonal DN T cells, which similarly do not appear to be enriched for true 'invariant' NKT cells or even other CD1d-restricted 'non-invariant' (or Type 2) NKT. C'est la vie !
Best,
Mark.
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