Characterising T Cell Exhaustion in Chronic HIV Infection - GSS 3.0 (4/5) - Wasihun Hailemichael

So you've worked on, I think, leishmaniasis, right?

Yes.

HIV infection.

So I work with people living with HIV on my study subjects.

And I look at the phenotypic changes of CD8 positive T cells.

We also call it CD8 positive T cell exhaustion, which is really described in various chronic viral infections, including HPV and HCV.

And also, of course, it's really known also in cancer that CD8-positive T-cells are exhausted.

And of course, in cancer, it's really quite worked out because the immune checkpoint blockage treatments are really mostly working in cancer.

So it's still ongoing or developing That could work in the same way for chronic viral infections such as HIV, but in cancer it's quite successful already, the immunotherapy that reinvigorates CD8 positive T cells.

Take us to what it means for the CD8.

T cell to be exhausted and maybe before that just tell us what CD8 positive T cells are

I recently had a presentation and I think I used this analogy of football to explain how CD8 positive T cells become exhausted and maybe I could also try to explain it that way so I take CD8 positive T cells as a visiting team and the host of course the host immune system will be the home team like in football and so when so when you had infection like influenza where the visit the the cd8 positive the home team could easily win the game so there are three outcomes when whenever you have infection first the host could win the game like in the context of acute infections like influenza then and of course the immune system wins and you have a resolution of the infection everything is fine the next outcome is um In some viruses like Ebola or smallpox, of course, the virus could also win the immune system and the host could die from the infection.

But there is a third outcome in context of chronic viral infections such as HIV, where the game really takes longer because the host is not be able to clear the virus.

The virus also not completely killing the host.

So this game going on for really longer time, the virus also finds a way to trick the host that they cannot hide within the immune system.

And this game really goes on for a really longer time and they persist.

So CD8 positive T cells also try to get rid of the infection for some time, but at some point they also become tired and exhausted.

So this kind of balance makes CD8 positive T cells to become dysfunctional and Also, the virus then persists for a longer time.

I think that way may be exponentially better to communicate it to a more broader audience, I think.

Yeah, so like in football match, you just keep playing and the game doesn't end and all the players get exhausted.

Tired, because, you know, in football, it's 90 minutes.

If it's 90 minutes, then the players become tired and they'll not be able to win the game as well.

if they don't get some uh changes or but i think in in a

typical game the two teams should be tired but now we have only the t cells getting tired do the viruses get tired as well is that like viral exhaustion i'm wondering

that's a good point because the virus they just want to stay within within the body right because they are using us um as a shield to replicate and to stay within the, because the virus is not really a living organism, so they become living organism when they are attached to something, right? To some living, another living organism.