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Credit: NIAID
A fundamental theory about how the thymus “educates” T cells appears to be wrong, according to research published in Nature Communications.
It’s known that stem cells leave the bone marrow and travel to the thymus to become one of two CD4 T-cell types: effector cells or regulatory T cells (Tregs).
One widely held concept of why the cells become one type or the other is that they are exposed to different ligands in the thymus, said Leszek Ignatowicz, PhD, of Georgia Regents University in Augusta.
But when he and his colleagues limited the cells’ exposure to only one ligand, the same mix of T cells still emerged.
“We asked a simple question, ‘Is it going to affect their development,’ and the answer was ‘no,’” Dr Ignatowicz said. “The cells still mature in the thymus, so something else must be determining it.”
The finding provides more insight into immunity that could one day enable a new approach to vaccines that steer the thymus to produce more of whatever T-cell type a patient needs: more effector cells if they have an infection or cancer, more Tregs if they have autoimmune diseases such as arthritis and multiple sclerosis.
“We could help steer the education process in the desired direction,” Dr Ignatowicz said.
To uncover their findings, he and his colleagues studied two types of mice, each expressing a single ligand in the thymus. The researchers thought one would prompt strong ligand binding and favor Treg development, and the other would favor a weaker ligand bond and effector cell development.
The mix of resulting T cells was the same as if both were exposed to the usual thousands of ligands, although the experiment did reveal one difference.
Ligands—and, eventually, bacteria and other invaders—get the attention of T cells by activating their receptors. Both CD4 T-cell types generally have the same receptors, but they are organized differently.
The researchers found that as long as the binding was weak, as it was in the first mouse, there was a lot of overlap in the receptors the ligand bound to in both T-cell types. However, in the second mouse, where the ligand prompted strong binding, there was far less overlap.
“We are now trying to find what causes that difference,” Dr Ignatowicz said. 
Credit: NIAID
A fundamental theory about how the thymus “educates” T cells appears to be wrong, according to research published in Nature Communications.
It’s known that stem cells leave the bone marrow and travel to the thymus to become one of two CD4 T-cell types: effector cells or regulatory T cells (Tregs).
One widely held concept of why the cells become one type or the other is that they are exposed to different ligands in the thymus, said Leszek Ignatowicz, PhD, of Georgia Regents University in Augusta.
But when he and his colleagues limited the cells’ exposure to only one ligand, the same mix of T cells still emerged.
“We asked a simple question, ‘Is it going to affect their development,’ and the answer was ‘no,’” Dr Ignatowicz said. “The cells still mature in the thymus, so something else must be determining it.”
The finding provides more insight into immunity that could one day enable a new approach to vaccines that steer the thymus to produce more of whatever T-cell type a patient needs: more effector cells if they have an infection or cancer, more Tregs if they have autoimmune diseases such as arthritis and multiple sclerosis.
“We could help steer the education process in the desired direction,” Dr Ignatowicz said.
To uncover their findings, he and his colleagues studied two types of mice, each expressing a single ligand in the thymus. The researchers thought one would prompt strong ligand binding and favor Treg development, and the other would favor a weaker ligand bond and effector cell development.
The mix of resulting T cells was the same as if both were exposed to the usual thousands of ligands, although the experiment did reveal one difference.
Ligands—and, eventually, bacteria and other invaders—get the attention of T cells by activating their receptors. Both CD4 T-cell types generally have the same receptors, but they are organized differently.
The researchers found that as long as the binding was weak, as it was in the first mouse, there was a lot of overlap in the receptors the ligand bound to in both T-cell types. However, in the second mouse, where the ligand prompted strong binding, there was far less overlap.
“We are now trying to find what causes that difference,” Dr Ignatowicz said.
Credit: NIAID
A fundamental theory about how the thymus “educates” T cells appears to be wrong, according to research published in Nature Communications.
It’s known that stem cells leave the bone marrow and travel to the thymus to become one of two CD4 T-cell types: effector cells or regulatory T cells (Tregs).
One widely held concept of why the cells become one type or the other is that they are exposed to different ligands in the thymus, said Leszek Ignatowicz, PhD, of Georgia Regents University in Augusta.
But when he and his colleagues limited the cells’ exposure to only one ligand, the same mix of T cells still emerged.
“We asked a simple question, ‘Is it going to affect their development,’ and the answer was ‘no,’” Dr Ignatowicz said. “The cells still mature in the thymus, so something else must be determining it.”
The finding provides more insight into immunity that could one day enable a new approach to vaccines that steer the thymus to produce more of whatever T-cell type a patient needs: more effector cells if they have an infection or cancer, more Tregs if they have autoimmune diseases such as arthritis and multiple sclerosis.
“We could help steer the education process in the desired direction,” Dr Ignatowicz said.
To uncover their findings, he and his colleagues studied two types of mice, each expressing a single ligand in the thymus. The researchers thought one would prompt strong ligand binding and favor Treg development, and the other would favor a weaker ligand bond and effector cell development.
The mix of resulting T cells was the same as if both were exposed to the usual thousands of ligands, although the experiment did reveal one difference.
Ligands—and, eventually, bacteria and other invaders—get the attention of T cells by activating their receptors. Both CD4 T-cell types generally have the same receptors, but they are organized differently.
The researchers found that as long as the binding was weak, as it was in the first mouse, there was a lot of overlap in the receptors the ligand bound to in both T-cell types. However, in the second mouse, where the ligand prompted strong binding, there was far less overlap.
“We are now trying to find what causes that difference,” Dr Ignatowicz said.