During infections, the immune system needs to distinguish strange antigens that are expressed by invasive bacteria and virus of autoantigens that are expressed by body cells. If not, the immune system can attack its own cells by mistake, causing damage durable to the tissue and a possible long -term disease.
A new research from the University of Chicago shows how a population of specially trained immune cells maintains peace by preventing other immune cells from attacking yours. The study, published in ScienceIt provides a better understanding of immune regulation during infection and could provide a basis for interventions to prevent or reverse autoimmune diseases.
Several groups of white blood cells help coordinate immune responses. Dendritic cells absorb strange pathogens proteins, cut them into peptides called antigens and show them on their surface. Conventional CD4+, or auxiliary T cells, inspect the peptides presented by dendritic cells. If peptides are strange antigens, T cells expand in number and transform into an activated state, specialized to eradicate the pathogen. If the dendritic cell carries a “self-feet”, or peptides of the body’s own tissue, T cells should be part of.
During an autoimmune response, auxiliary T cells do not distinguish between strange peptide antigens and properly self-peppers and perform the attack regardless of what. To prevent this from happening, it is assumed that another group of T called T cells CD4+ (TREG) regulators intervene and avoid the friendly fire of Tconv cells.
“You can think of them [Treg cells] Like the cells of La Paz, “said Pete Savage, PHD, a professor of pathology at Uchicago and main author of the new study. Trets obviously does his job well most of the time, but Savage said he has never been clear how they know when they intervene and prevent auxiliary T cells from eating a self -immune response, and when to stop and let them fight for an infection.
Then, Savage and his team, led by David Klawon, PHD, a former student graduated in his laboratory who is now a postdoctoral member at MIT, wanted to explore this property of the immune system, known in the field as discrimination to herself. T cells are produced in the thymus, a specialized organ of the immune system. During development, TREG cells are trained to recognize specific peptides, including body’s highways. When dendritic cells have a self-feet, treg cells trained to detect them intervene to prevent assistant T cells being activated.
This specificity is what Savage’s team found makes a crucial difference in self -discrimination. The researchers experimentally exhausted the TREG cells in mice that were specific to a single self-topid of the prostate. In healthy mice in the absence of infection, this change did not trigger self -immunity to the prostate. However, when the researchers infected mice with a bacterium that expressed the prostate self-spit, the absence of specific prostate TREG cells triggered T-helper cells reactive for the prostate and introduced the autoimmunity into the prostate.
Interestingly, this alteration did not affect the capacity of auxiliary T cells to control bacterial infection responding to strange peptides.
“It is like a population of T Doppelger cells. CD4 auxiliary cells that could induce diseases attacking auto -part an equivalent and equal population of these TREG TREG cells,” Savage said. “When we eliminate the treg reactive cells to a single self-feet, T-helper cells reactive to that self-peptide no longer controlled and induced autoimmunity.”
The root causes of autoimmune disease are a complex interaction of genetics, the environment, lifestyle and the immune system. Classical and conventional thinking in the field of immunology promoted the idea that the immune system establishes discrimination to itself by purging the body of the auxiliary T cells that are reactive to the highways, thus avoiding self -immunity. However, Savage said that this study shows that purge is inefficient and that the specificity that coincides with TREG cells can be equally important.
“The idea is that specificity is important, and for a completely healthy immune system, you must have a good collection of these TREG Doppelger cells,” he said. While the immune system generates enough coincidental cells, they can prevent autoimmune responses without affecting the responses to infections.
“It’s like turning the idea of discrimination to itself. Instead of having to eliminate all Auxiliary T cells reactive to autoantigens, it simply generates enough of these Tret Pealkeeper cells,” Savage said.