Hope for HIV patients - way found to revive immune cellsNovember 11th, 2008 - 12:23 pm ICT by IANS
Toronto, Nov 11 (IANS) There is new hope for Acquired Immuno Deficiency Syndrome (AIDS) patients as Canadian and American researchers have discovered a way to revive the body’s tired immune cells in their fight against the Human Immunodeficiency Virus (HIV) that leads to AIDS.Researchers at the University of Toronto and the University of California in San Francisco say their discovery of a way to “revive” immune cells that are exhausted from fighting HIV infection opens up the possibility of new therapies for HIV patients.
As part of their research, the joint team led by Mario Ostrowski of the University of Toronto and Douglas Nixon of the University of California discovered the large-scale presence of a molecule called Tim-3 on immune system cells which are “exhausted” from fighting HIV infection.
The researchers found that blocking the activity of Tim-3 on these cells improved their (cells’) function and allowed them to rejoin the battle against HIV, a University of Toronto statement said.
“In the typical course of HIV infection, an initial burst of very high levels of the HIV virus is brought partially under control by the infected person’s immune system, specifically by an immune system cell called a CD8+ killer T cell.
“In the majority of cases without antiretroviral drug treatment, the immune system is eventually overwhelmed and progression to AIDS occurs,” said research co-principal author Brad Jones.
Explaining how progression to AIDS is associated with a breakdown in those CD8+ T immune system cells, the researchers said that in a typical viral infection, those cells rapidly multiply, kill off virus-infected cells and stimulate other cells in the immune system.
Over time, in the battle to fight off HIV infection, CD8+ T cells become less functional and enter into a state known as “exhaustion”.
Since the mechanisms that lead to their exhaustion are not known, Jones said: “We felt that if we could understand these mechanisms, we may be able to intervene and re-energise the immune system.”
Further research led the team to believe that this exhausted state may result from the Tim-3 molecule sending a signal to shut down CD8+ T cells in HIV-infected individuals.
In support of their theory, the team found that Tim-3 expression on T cells, in particular the CD8+ T cells, was keeping with clinical parameters of HIV progression in a diverse group of individuals.
“From these results, we predicted that the Tim-3 pathway might be manipulated to potentially confer clinical benefit and serve as a promising new target for clinical intervention to decrease the severity of HIV infection,” said research co-principal author Lishomwa Ndhlovu.
“To test this, we produced a molecule capable of blocking the Tim-3 signal and studied the effect that this had on CD8+ T cell function in vitro,” said Ostrowski.
“We observed that blocking the Tim-3 pathway rescued those cells and restored their ability to fight off infection,” he added.
The researchers said they still do not know how the virus triggers Tim-3 or if this is restricted to HIV infection.
“But our findings may provide a new direction to vaccines and therapies that will potentially reverse these dysfunctional cells and allow them to control HIV-1 replication,” said Ndhlovu.
The study has been published in the Nov 24 issue of the Journal of Experimental Medicine.