Immune T cells are programmed to recognize different microbes
that may cause infection. When this happens responding T cells are
'activated', and increase in number by dividing. The number of cells
formed and how long they live is tightly controlled to ensure the
infection can be successfully fought and any excess immune cells are
cleared out of the body.
An Australian research team has revealed that two internal 'clocks'
control the immune cells enlisted to fight infection. This discovery
upends previous theories on how immune responses are regulated.
‘During an immune response two internal 'clocks' allocate a certain amount of time in which the cells can divide, as well as prescribing the cells' lifespan.’
The team discovered that during an immune response the clocks
allocate a certain amount of time in which the cells can divide, as well
as prescribing the cells' lifespan. The finding sheds new light on how
the body controls immune responses, as well as explaining how immune
cell cancers such as leukemia and lymphoma maybe caused by errors in
Dr. Susanne Heinzel and Professor Phil Hodgkin led a Walter and
Eliza Hall Institute research team that investigated how these two
processes - division and clearance - are controlled, in research
published in Nature Immunology
Dr. Heinzel said the team discovered activated T cells in an
immune response are programmed to divide for a limited time. "We had
previously shown the number of cells a 'parent' T cell produces is
tightly regulated," she said. "The suspicion was the T cell 'knows' how
many times it can divide. We were stunned to find this wasn't the case -
the T cell is given an amount of time in which it can divide, like a
clock running," she said. "Once this time is up, no more divisions can
"Intriguingly, as well as being allocated a certain amount of
time in which to divide, early in an infection, we found T cells
separately set their lifespan, how long they and their offspring live.
After this time expires, the cells undergo apoptosis, a form of cell
suicide," Dr Heinzel said.
Professor Hodgkin said the team built on their discovery of the
two-clock system by pinpointing a protein called Myc that acts as the
cell division clock. "At the start of an immune response, responding T
cells are allocated a certain amount of Myc," he said. "This diminishes
over time, and once the cell runs out of Myc, time's up and division
stops. The more Myc there is, the more time the cells have to divide.
"We also showed the lifespan clock is controlled by a protein
called Bcl-2 - when this time runs out the cells die, whether or not
they've come to the end of their division clock," he said.
Dr. Heinzel said the research provided new insights into how
complex immune responses are controlled, and the fine balance between
normal cell division and cancerous cell growth. "The two clocks are an
elegant way that our body governs how many responder cells are produced
in an immune response, and how long they are retained," she said. "Small
changes in each clock combined to substantially alter immune cell
"It has been known for many years that excess Myc and Bcl-2 are
important contributors to cancer formation. Our findings explain how a
small series of mutation-driven changes in healthy immune responses
could lead to immune cell cancers such as leukemia and lymphoma," she