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Edward Nirenberg @enirenberg.bsky.social · 15h

6. MMR is a 2-dose series. But yes.

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Edward Nirenberg @enirenberg.bsky.social · 1d

Monovalent vaccines already exist for other parts of the world.

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Edward Nirenberg @enirenberg.bsky.social · 1d

Just to recap:
- There is no demonstrated benefit to the safety or effectiveness of MMR by giving it separately as single-virus vaccines
- Countries that have tried this have ended up with outbreaks of measles/mumps/rubella because it's harder for people to complete the series

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Edward Nirenberg @enirenberg.bsky.social · 1d

I don't know who was nominated but I doubt that he could be for the category of Medicine

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Edward Nirenberg @enirenberg.bsky.social · 1d

This serves absolutely no purpose other than to reduce vaccine uptake:
www.reuters.com/business/hea...

www.reuters.com

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Edward Nirenberg @enirenberg.bsky.social · 1d

it's still important!

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Edward Nirenberg @enirenberg.bsky.social · 1d

I can't say with certainty. CTLA-4 was discovered well before regulatory T cells were defined.

rupress.org/jem/article/...

CTLA-4 is a second receptor for the B cell activation antigen B7.

Functional interactions between T and B lymphocytes are necessary for optimal activation of an immune response. Recently, the T lymphocyte receptor CD28 wa

rupress.org

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Edward Nirenberg @enirenberg.bsky.social · 1d

This is James Allison's work. He already won a Nobel for it:
www.nobelprize.org/prizes/medic...

Nobel Prize in Physiology or Medicine 2018

The Nobel Prize in Physiology or Medicine 2018 was awarded jointly to James P. Allison and Tasuku Honjo "for their discovery of cancer therapy by inhibition of negative immune regulation"

www.nobelprize.org

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Edward Nirenberg @enirenberg.bsky.social · 1d

Oh- for those who want to learn about regulatory T cells in more detail, there are these reviews:
rdcu.be/eJHTr

rdcu.be/eJHU8

www.sciencedirect.com/science/arti...

www.annualreviews.org/content/jour...

The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases

Nature Reviews Immunology - In this Review, the authors discuss the origins of regulatory T (Treg) cells in the periphery and the mechanisms by which Treg cells are induced, as well as the...

rdcu.be

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Edward Nirenberg @enirenberg.bsky.social · 1d

rdcu.be/eJHTr

rdcu.be/eJHU8

www.sciencedirect.com/science/arti...

www.annualreviews.org/content/jour...

The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases

Nature Reviews Immunology - In this Review, the authors discuss the origins of regulatory T (Treg) cells in the periphery and the mechanisms by which Treg cells are induced, as well as the...

rdcu.be

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Edward Nirenberg @enirenberg.bsky.social · 1d

In short, regulatory T cells are an incredibly important part of the immune system, and learning about them has led to breakthrough therapies in clinic.

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Edward Nirenberg @enirenberg.bsky.social · 1d

We also have antibodies against CD28 (the receptor that CTLA-4 competes with that has an activating function) to manage certain autoimmune diseases or prevent transplant rejection:
www.nejm.org/doi/full/10....
www.sciencedirect.com/science/arti...

Phase III Study of Belatacept Versus Cyclosporine in Kidney Transplants from Extended Criteria Donors (BENEFIT‐EXT Study)

Recipients of extended criteria donor (ECD) kidneys are at increased risk for graft dysfunction/loss, and may benefit from immunosuppression that avoi…

www.sciencedirect.com

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Edward Nirenberg @enirenberg.bsky.social · 1d

in the setting of cancer, which maintains an immunosuppressive tumor microenvironment to prevent elimination by the immune system. We now have antibodies against CTLA-4 used for cancer treatment (immune checkpoint inhibitors):
www.nejm.org/doi/full/10....

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma | NEJM

An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to ...

www.nejm.org

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Edward Nirenberg @enirenberg.bsky.social · 1d

Clinically, understanding peripheral tolerance has been critical to multiple treatments now available. For example, to restrain immune responses, regulatory T cells express a protein called CTLA-4. When T cells recognize this protein, it blocks their activation. This, however, can be a problem...

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Edward Nirenberg @enirenberg.bsky.social · 1d

In this condition, people have no functional regulatory T cells and consequently (mostly) cannot restrain immune responses from causing tissue damage, leading to hyperactive inflammation and autoimmune disease. This is an extremely severe condition and requires a bone marrow transplant to treat.

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Edward Nirenberg @enirenberg.bsky.social · 1d

To program a T cell to be a regulatory T cell requires the action of a transcription factor (a protein that turns genes on or off) called FoxP3. In 2001, Mary Brunkow and Fred Ramsdell identified that IPEX syndrome was caused by mutations in FoxP3:
rdcu.be/eJHEr

The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3

Nature Genetics - The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3

rdcu.be

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Edward Nirenberg @enirenberg.bsky.social · 1d

A lot of peripheral tolerance relies on a cell type called the regulatory T cell. In essence, rather than attacking when activated, regulatory T cells suppress immune responses to curb tissue damage. These were discovered by Nobel winner Shimon Sakaguchi in 1995:
academic.oup.com/jimmunol/art...

Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases

Abstract. Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor α-chain (CD2

academic.oup.com

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Edward Nirenberg @enirenberg.bsky.social · 1d

Peripheral tolerance essentially refers to the mechanisms that keep the immune system in check once those cells that recognize self have been made. There are a LOT of mechanisms involved here, generally they work really well. Peripheral tolerance is actually more important than central tolerance.

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Edward Nirenberg @enirenberg.bsky.social · 1d

to self, which can (but is not guaranteed to) trigger autoimmune disease. We also make antibodies that naturally react to a bunch of things (so-called natural IgM), which might include self. For this reason, the immune system has a complex set of mechanisms known as peripheral tolerance.

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Edward Nirenberg @enirenberg.bsky.social · 1d

or get an opportunity to change their binding specificity (for B cells). The problem with central tolerance is that it's really leaky. T cells have to be able to recognize proteins called MHC (which present antigens to them), so they are selected for this. That gives you T cells that might react...

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Edward Nirenberg @enirenberg.bsky.social · 1d

Self-tolerance is the capacity of your immune system not to attack your own body. The mechanisms by which this occurs are split into central and peripheral tolerance.

Central tolerance ensures that B and T cells that react to ourselves die, get shifted to a regulatory fate (for T cells)...

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Edward Nirenberg @enirenberg.bsky.social · 1d

This year's Nobel Prize in Physiology or Medicine was just announced:
www.nobelprize.org/prizes/medic...

This seems like a good opportunity for me to explain a bit about peripheral immune tolerance and where the prizewinners' work comes in 🧵

6 October 2025

The Nobel Assembly at Karolinska Institutet has decided to award the 2025 Nobel Prize in Physiology or Medicine to:

Mary E. Brunkow
Institute for Systems Biology,
Seattle, USA

Fred Ramsdell
Sonoma Biotherapeutics,
San Francisco, USA

Shimon Sakaguchi
Osaka University,
Osaka, Japan

“for their discoveries concerning peripheral immune tolerance”

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Reposted by Edward Nirenberg

Prof Peter Hotez MD PhD DSc(hon) @peterhotezmdphd.bsky.social · 5d

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Edward Nirenberg @enirenberg.bsky.social · 2d

Yeah. It’s generally not serious in the life threatening sense but it can be quite bad. Especially with secondary skin infections from the scratching

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Edward Nirenberg @enirenberg.bsky.social · 2d

I think it’s too early for it to move the needle with most places that aren’t doing it already (although I agree). That said, zoster for elderly + varicella for kids solves any theoretical concerns

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