Yeah, I originally was trying to figure out a mechanism for increasing CD-8 T-cells (via TReg inhibition perhaps allowing CD-8 T-cells to be created at a higher rate from progenitor cells) when Dr. Patterson on Dr. Drew said:
https://www.youtube.com/watch?v=JRhICdnPMpc
at 6-10.5 minutes or so
"CCR5 able to increase CD8 T-cells ... suppressed in these critical patients"
" CCR5 blockade could bring back the CD8 count, keep them from being sequestered solely in the lungs , brought back T-cell function"
"Fine line between good effects and bad effects"
"density of CCR5" on different cell types
"inhibiting the bad cells (TRegs) and allowing the good cells to still function (CD8) .. part of the strategy for cancer"
Dr. Drew at 9:45: "Do you have a theory for why the CD8s come up?"
BP: "I truly believe it's basically redistribution. I mean obviously it's not stimulating the production of more CD8s, but I think what we're doing is inhibiting to some extent the sequestration of all the CD8s in the heavily inflamed lungs and we're allowing the CD8s to increase in the peripheral blood and to perform normal functions elsewhere ."
Hard to know. Immunology is pretty complicated. But I trust Bruce Patterson for the most part.
I agree also with the two potential mechanisms you listed.
EDIT: More of the "transcript" here:
"ccr5 as a as a co-receptor for hiv entry when in fact it has a very elegant i've called it the quarterback of the immune system because it's really responsible for getting the necessary immune cells where they need to be and they're expressed in a wide range of immune cells what's interesting is they're expressed on cells that have uh antagonistic functions so ccr5 is expressed on effector t cells which are the ones that fight off virally infected cells or cancer like so-called killer t cells yeah yeah killer t cells and then they're also expressed in a cell called the t regulatory cell which shuts off the immune system so that you don't go on to have an autoimmune response so you know it's it's a fine balance with ccr5 between its good effects and potentially bad effects but i think that really comes down to the density of ccr5 on these particular cells and by knowing that we're able to manipulate the immune system to be more favorable by inhibiting the bad cell and and allowing the good cells uh to still function and i think that's that's also part of the you know the the strategy for cancer."
So we want TRegs to be inhibited more than CD-8 T-cells in cancer and Covid (to keep the TRegs away and allow the CD-8 T-cells in to kill the infected or cancer cells), but in auto-immune diseases, we want the TRegs to go to the site of inflammation and want the CD-8 T-cells to stay away.
I'm not sure how one drug could do both things. It will be interesting to find out if it can, and how.
https://www.youtube.com/watch?v=JRhICdnPMpc
at 6-10.5 minutes or so
"CCR5 able to increase CD8 T-cells ... suppressed in these critical patients"
" CCR5 blockade could bring back the CD8 count, keep them from being sequestered solely in the lungs , brought back T-cell function"
"Fine line between good effects and bad effects"
"density of CCR5" on different cell types
"inhibiting the bad cells (TRegs) and allowing the good cells to still function (CD8) .. part of the strategy for cancer"
Dr. Drew at 9:45: "Do you have a theory for why the CD8s come up?"
BP: "I truly believe it's basically redistribution. I mean obviously it's not stimulating the production of more CD8s, but I think what we're doing is inhibiting to some extent the sequestration of all the CD8s in the heavily inflamed lungs and we're allowing the CD8s to increase in the peripheral blood and to perform normal functions elsewhere ."
Hard to know. Immunology is pretty complicated. But I trust Bruce Patterson for the most part.
I agree also with the two potential mechanisms you listed.
EDIT: More of the "transcript" here:
"ccr5 as a as a co-receptor for hiv entry when in fact it has a very elegant i've called it the quarterback of the immune system because it's really responsible for getting the necessary immune cells where they need to be and they're expressed in a wide range of immune cells what's interesting is they're expressed on cells that have uh antagonistic functions so ccr5 is expressed on effector t cells which are the ones that fight off virally infected cells or cancer like so-called killer t cells yeah yeah killer t cells and then they're also expressed in a cell called the t regulatory cell which shuts off the immune system so that you don't go on to have an autoimmune response so you know it's it's a fine balance with ccr5 between its good effects and potentially bad effects but i think that really comes down to the density of ccr5 on these particular cells and by knowing that we're able to manipulate the immune system to be more favorable by inhibiting the bad cell and and allowing the good cells uh to still function and i think that's that's also part of the you know the the strategy for cancer."
So we want TRegs to be inhibited more than CD-8 T-cells in cancer and Covid (to keep the TRegs away and allow the CD-8 T-cells in to kill the infected or cancer cells), but in auto-immune diseases, we want the TRegs to go to the site of inflammation and want the CD-8 T-cells to stay away.
I'm not sure how one drug could do both things. It will be interesting to find out if it can, and how.
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