One of the coolest things I learned last week in Banff is the ‘why’ behind an odd AIDS phenomena:
So you all might know that the cut-off, the mark for being diagnosed with AIDS (and not just ‘HIV-1+’) is a CD4+ T-cell count of <200 cells/mm3. Okay, so, you lose all your CD4+ T-cells, your immune system loses its ability to work properly, and you start getting all these secondary infections— infections that ‘healthy’ people get, but they arent a big deal. But secondary infections are a big deal to AIDS patients, I mean, thats what they die of, not the HIV-1 specifically.
What is weird, is that HIV-1+ patients get Tuberculosis before they hit that ‘200 cells/mm3’ mark. In fact, its one of the first signs of HIV-1 infection, a random ‘healthy’ person getting TB. Conversely, Cytomegalovirus doesnt reactivate until you are waaaaay below 200. You dont lose your ability to defend yourself against CMV until you are basically running on empty.
It appears as if the CD4+ T-cells that ‘remember’ TB are more susceptible to HIV-1 infection, while CD4+ T-cells that ‘remember’ CMV are protected from HIV-1 infection.
But how the heck would that work??
CD4+ T-cells that ‘remember’ TB secrete chemical messages that keep them in more of an ‘active’ state… precisely the kind of cell HIV-1 LOVES to infect.
On the other hand:
CD4+ T-cells that ‘remember’ CMV secrete chemical messages that are protective, mainly, one called MIP-1β. MIP-1β is the ligand to CCR5, one of the co-receptors HIV-1 needs to infect cells. So if MIP-1β is taking up all the available CCR5 slots, or the bounty of MIP-1β around causes the cell to downregulate CCR5, those cells would be protected from HIV-1 infection!
Similar research from another lab backs this up:
This has a huge impact on how we design HIV-1 vaccines! What would be the point in making a vaccine against HIV-1, if all your CD4+ T-cells that ‘remember’ HIV-1 are killed off in the first round of HIV-1 infection?
So now all we have to do is figure out how to make a vaccine that generates CMV-like CD4+ T-cells, not TB-like cells! Easy-peasy… right?