Scientists Question Fundamental Theory about Education of Immune Police

A new study reveals that the fundamental theory that has long been believed in about how the thymus gland of our body educates our immune police seems to be wrong.

It has been long known that the stem cells emerge from the bone marrow and travel to the thymus gland that is situated behind the breastbone in order to learn to become one of two CD4T cell types. One of them leads an attack and the other one keeps the peace.

Dr. Leszek Ignatowicz, immunologist at the Medical College of Georgia at Georgia Regents University remarked that the widely held concept about why they become one of the either types even though they come from the same neighborhood and attend the same school is that. They are exposed to different ˜things' in the thymus. The ˜things' we are talking about are called the ligands. The developing T cells are exposed to several hundred tiny pieces when inside the thymus gland.  Ligands are unique, just like our fingerprints. However, when the researchers limited exposure to only one fingerprint, the T cell mix that emerged was the same.

Ignatowicz said that they focussed on a simple question and that was – if it was going to affect their development and the answer was no.  Ignatowicz opined that since the cells still mature in the thymus, so there must be something else which is determining it. The finding is significant as it can pave way for providing more insight into immunity which could one day enable a new approach to vaccines which makes the thymus gland to produce more of whatever T cell type a particular patient needs. Say, one has a bad infection or cancer more effector cells are needed, in case of autoimmune diseases such as arthritis, multiple sclerosis, etc., more regulatory T cells are needed. It is possible for us to steer the education process in the desired direction.

Learning experience in the thymus is a tough experience. It is observed that the majority of the T cells either learn to be too aggressive or too passive. That is why they never make it out of the thymus. It is also seen that as much as 95% of the T cells that survive eventually becomes effector cells who are someday responsible for driving the response of the immune system to invaders such as bacteria, viruses, and tumors. The effector cells learn to recognize invaders happens when they are out roaming the body.

Dr. Richard A. McIndoe, a bioinformatics expert and Associate Director of the MCG Center of Biotechnology and Genomic Medicine explained that these future aggressors are the ones which bind less strongly to ligands they experience in the thymus. It is not desirable for an effector cell that binds strongly to oneself because that would make it attack the body itself he explained.

In order to conduct this study, the scientists experimented on two mice. Each of them expressed a single ligand in the thymus – the researchers had assumed that it would prompt strong binding. And another one was that would favor a weaker bond and effector cell development.

The mix of resulting T cells was the same “ the setting was such both were exposed to the usual thousands of ligands however, there was a difference. Ligands “ and eventually bacteria and other such invaders are noticed T cells by activating their receptors. It was seen both CD4T cell types generally have the same receptors, just organized differently. The finding of MCG scientists was that as long as the binding was weak – like it was in the first mouse, there was a lot of overlap in the receptors the ligand bound to in both T cell types. But, in the case of second mouse, which should have favored Treg development because the ligand prompted strong binding, there was significant less overlap.

The task now is to find out what causes that difference remarked Ignatowicz.

References

https://www.eurekalert.org/pub_releases/2014-10/mcog-sqf100814.php

https://www.sciencedaily.com/releases/2014/10/141008131609.htm