Scimex: An Australian research team has revealed that the immune cells enlisted to fight infections in our body are under the control of two internal ‘clocks’, upending previous theories on how immune responses are regulated. 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 cancers such as leukaemia and lymphoma maybe caused by errors in this system.
Immune T cells are programmed to recognise different microbes. When
this happens during an infection the responding T cells are ‘activated’,
and increase in number by dividing. Tight controls on how many cells
are formed and how long they survive ensure the infection can be
successfully fought, but that the excess immune cells are cleared so
they do not overwhelm our body.
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 on
Tuesday 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 happen.
“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
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 leukaemia and lymphoma,” she
The research was supported by the Australian National Health and
Medical Research Council, an Australian Postgraduate Award, the Edith
Moffat Scholarship, Melbourne International Research and International
Fee Remission Scholarships, Cancer Council Victoria, the Alan Harris
Scholarship Fund, and the Victorian Government Operational
The Walter and Eliza Hall Institute is the research powerhouse of the
Victorian Comprehensive Cancer Centre, an alliance of leading Victorian
hospitals and research centres committed to controlling cancer.