GMO CTLs vs HIV

This is just another excuse to poke fun at the stupidity of Creationists–

Creationists try to lecture us all the time about how ‘perfect’ our immune system is. How wonderful and precise and intelligently designed it is obviously points towards the existence of a creator god (aka the Christian god).

Well, if our immune system is the best their god can do, then we should all be worshiping HIV-1, because its ‘smarter’. Its been outwitting our immune systems for well over a century, and outwitting some of the best thinkers of our time and the best technology we have to offer for three decades.

But HIVs number might be up very soon.

With a combination of knowledge, technology, and insanity, scientists (including myself) are subverting our immune systems ‘natural’ processes, and genetically modifying cells to have the ‘right’ answer to HIV-1. The immune system no longer has to bumble, stumble, blindly get itself caught in a corner, trying to find the ‘right’ answer to a pathogen.

We can tell the immune cells the right answer.

A group of scientists just published one way of doing that:

In Vivo Suppression of HIV by Antigen Specific T Cells Derived from Engineered Hematopoietic Stem Cells

Longtime readers of ERV are acquainted with CTLs and their relationship with HIV-1.

Briefly, there are ‘flags’ that are on the surface of all of your cells that tell your CD8+ T-cells (Cytotoxic T-cells, CTLs) what proteins it is making. The CTLs know what is ‘normal’. If they see a protein flag that is not ‘normal’, eg a viral protein, they gently persuade the infected cell to commit suicide.

But CTLs do not recognize SELF, NONSELF in a binary manner. CTLs dont see SELF at all. CTLs have a receptor, TCR, that can only see a very specific NONSELF. If that NONSELF matches up with something HIV-1 makes, and that CTL ‘sees’ an HIV infected cell, the infected cell dies.

So this means that to get rid of all the HIV-1 infected cells, you have to have the right CTLs that can see the HIV-1 protein, at the right place (who cares if the right CTL is in the liver, when the HIV infected cells are in the thymus), at the right concentration (who cares if you have one right CTL at the right place if there are 10^6 infected cells and counting).

And then theres HIV-1 itself. It has the ability to change the protein the CTL can see to a different protein that the CTL cant see.

Is it any wonder that CTLs have a rough time clearing HIV-1 infection.

So these folks got an idea: Lets genetically modify cells to give the immune system a LOT of the ‘right’ CTLs.

Basically, they want to Zerg rush HIV with anti-HIV CTLs.

To test this, they used a humanized mouse model (mouse with a human-like immune system, because mice cannot be infected with HIV-1). Some of the mice they left alone, some they infected with HIV-1, and some they infected with HIV-1 AND genetically modified the immune cells to express the anti-HIV receptor.

The mice that got the ‘right’ anti-HIV receptor had about half the number of infected cells as the mice with immune systems that were left to figure out things on their own.

The mice that got the ‘right’ anti-HIV receptor were also able to maintain much higher CD4 counts over time (though as time went on, they still dropped far below normal).

So, is this paper good? Yup!

Is it a cure for HIV-1 infection? Nope!

This paper is a cool step in a novel direction. There are still lots of caveats (you would have to tailor the genetic modification for everyones particular HLA type, HIV-1 would undoubtedly evolve around this, as it already has in nature), but the HIV field needs to take steps in new directions, however small they might be.

Comments

  1. #1 JustaTech
    April 17, 2012

    This is so cool! But why oh why can’t immunologists be satisfied with a single set of terminology? Why CD8+T-cell and CTL? And why are half the CDs called by some other, old name? think how much more progess could be made if you didn’t have to spend half your time looking up the other name!

  2. #2 ToSeek
    April 17, 2012

    Aren’t there at least a half-dozen ways our own immune systems can kill us? Not to mention all the ways it just makes us miserable?

  3. #3 Bryan
    April 18, 2012

    But why oh why can’t immunologists be satisfied with a single set of terminology? Why CD8+T-cell and CTL?
    Because not all CTL’s (cytotoxic lymphocytes) are CD8+, nor are all CD8+ cells are CTL’s.

    Bryan

  4. #4 cynical1
    April 18, 2012

    “But CTLs do not recognize SELF, NONSELF in a binary manner. CTLs dont see SELF at all. CTLs have a receptor, TCR, that can only see a very specific NONSELF.”

    What about autoimmunity? Those CTLs wreck havoc in those diseases, right?

  5. #5 Tony Mach
    April 23, 2012

    First link is broken, I think it should go here:
    http://scienceblogs.com/erv/2011/07/hiv-1_ctl_vaccine_did_hiv.php

  6. #6 Tony Mach
    April 23, 2012

    Sorry, meant second link.

  7. #7 Rhology
    April 23, 2012

    Creationists try to lecture us all the time about how ‘perfect’ our immune system is. How wonderful and precise and intelligently designed it is obviously points towards the existence of a creator god (aka the Christian god).

    Um, who precisely says anything of the kind?

  8. #8 123
    April 23, 2012

    We can look high or we can look low, in books or in journals, but the result is the same. The scientific literature has no answers to the question of the origin of the immune system. (Behe, Darwin’s Black Box, p. 138)

    Other examples:

    The Intelligent Design of the Immune System : On this episode of ID the Future, Dr. Donald L. Ewert continues to explain why the vertebrate adaptive immune system does not use “random” or “chance” processes like Darwinian evolution to generate antibody diversity. Instead, he argues that the immune system is intelligently designed.

    The Immune System: Our amazing immune system defies evolutionary origin. Blood antibodies, the heroes, are equipped to (1) recognize and (2) destroy the antigens (germs) and still (3) tolerate the organism’s own components. The only way antibodies can destroy the foe is to have a matching molecular structure. This requires a tremendous diversity of antibodies to fit the many shapes of antigens. Since all of the system works or none of it works, evolution requires the simultaneous development and operation of all four of these critical factors before natural selection can preserve it. Besides that, when our immune system encounters something for which it has no matching molecular structure, it manufactures the precise structure in a way similar to a locksmith honing in on the right combination. The immune system couldn’t just happen!

    Creotardation isn’t limited to Xtians, either!