Longterm Immune Memory Cells, cells do not develop during chronic viral infections

[Guest guest]

>

> Longterm immune memory cells cells do not develop

> during chronic viral

> infections

> 06 Nov 2004

>

>

>

<http://www.medicalnewstoday.com/medicalnews.php?newsid=15950>

>

http://www.medicalnewstoday.com/medicalnews.php?newsid=15950

> Finding by Emory University scientists has

> implications for vaccines,

> antiviral therapies and cancer treatment

>

> Immune T cells that respond to chronic viral

> infections do not acquire

> the same " memory " capabilities of T cells that

> respond to acute viral

> infections, according to research by scientists at

> Emory University.

> The finding may explain why people lose their

> immunity to some viruses

> after chronic infections are controlled. It could

> guide scientists in

> developing better therapeutic combinations of

> antiviral therapies and

> therapeutic vaccines. The research is published

> online in the

> Proceedings of the National Academy of Sciences.

>

> Lead author of the study is E. Wherry, PhD,

> postdoctoral fellow

> in the Department of Microbiology and Immunology at

> Emory University

> School of Medicine and the Emory Vaccine Center.

> Senior author is Rafi

> Ahmed, PhD, director of the Emory Vaccine Center,

> Georgia Research

> Alliance Eminent Scholar, and professor of

> microbiology and

> immunology.

>

> The immune system responds to viral infections in

> two ways: with

> antibodies that help prevent viruses from entering

> cells and with T

> cells activated in response to viral antigens. T

> cells kill the

> virus-infected cells and produce proteins called

> cytokines that

> prevent the growth of viruses and make cells

> resistant to viral

> infection. During the acute phase of a viral

> infection, activated CD8

> T cells respond aggressively for a few weeks, then

> about five percent

> of them become " memory cells " that maintain a stable

> memory T cell

> population by slow, steady turnover. These memory

> cells are poised to

> mount an even stronger and more rapid response to

> future attacks by

> the same virus. Individuals who acquire immunity to

> diseases such as

> measles, yellow fever, smallpox, or polio, either

> through exposure or

> vaccination, often are capable of retaining that

> immunity for many

> years or for an entire lifetime.

>

> Dr. Ahmed and his colleagues discovered in previous

> research that

> following acute viral infections, immune memory CD8

> T cells continue

> to maintain their ability to attack viruses even

> when they are not

> continuously stimulated by viral antigen (Science,

> Nov. 12, 1999).

> Other studies have suggested, however, that during

> some chronic

> infections continuing exposure to viral antigen may

> be necessary to

> maintain protective immunity.

>

> The Emory researchers used a mouse model of

> infection with lymphocytic

> choriomeningitis virus (LCMV) to study the

> differences in CD8 memory T

> cell immune response following acute and chronic

> infections. In mice

> with the acute infection, the virus was cleared by a

> CD8 T cell immune

> response within one week. In mice with the chronic

> infection, high

> virus levels were present in multiple tissues for

> the first two to

> three months, then the virus was controlled in most

> tissues by a T

> cell response but was not completely eliminated.

>

> To directly compare the memory capabilities of cells

> from both types

> of infection, the scientists transferred both acute

> memory and chronic

> memory CD8 T cells into uninfected mice, without

> transferring any of

> the viral antigen. The acute memory cells were

> maintained through

> homeostasis and divided several times, but the

> chronic memory cells

> failed to divide and declined in number over time.

> When the chronic

> memory CD8 T cells were transferred back into

> chronically infected

> mice where they re-encountered antigen, the cells

> began to recover.

>

> The scientists also compared other important

> qualities of memory T

> cells, including the responsiveness to cytokine

> signaling by

> interleukin 7 (IL-7) and interleukin 15 (IL-15).

> Response to these

> cytokines is a critical part of the immune pathway

> that allows memory

> CD8 T cells to undergo homeostatic division and to

> persist even in the

> absence of viral antigen. They found that chronic

> memory CD8 T cells

> responded poorly to both IL-7 and IL-15, whereas

> acute memory CD8T

> cells proliferated in response to both cytokines.

> Additional research

> could show whether the defect in chronic memory cell

> response to IL-7

> and IL-15 can be overcome by increasing the

> expression of these

> cytokines, or whether other deficiencies in the

> pathway exist.

>

> " The normal memory CD8 T cell differentiation

> program that occurs

> after acute infection results in memory cells that

> are capable of

> long-term persistence in the absence of antigen as a

> result of slow

> homeostatic proliferation in response to IL-7 and

> IL-15, " said Dr.

> Ahmed. " We have shown that during chronic LCMV

> infection this memory

> pathway does not proceed efficiently and that

> virus-specific CD8 T

> cells do not acquire the cardinal property of

> antigen-independent

> persistence. "

>

> The Emory scientists also concluded that rest from

> antigen exposure is

> an important criterion for developing long-term

> immune memory. Acute

> memory T cells are exposed to antigen for a finite

> time period after

> an acute infection, then after the virus with

> antigen is eliminated,

> these cells differentiate into memory T cells. A

> recent study of HIV

> infection showed that if antiretroviral therapy is

> initiated during

> the early phase of infection, HIV-specific CD8 T

> cells are maintained

> more efficiently.

>

> " Our research shows that prolonged exposure to

> antigen without any

> rest results in cells that are " addicted " to antigen

> and cannot

> persist without it, " Dr. Ahmed explains. " This

> raises concerns about

> vaccine strategies that use persisting antigen,

> because

> antigen-independent memory T cells may not develop. "

>

> The study may help explain the loss of T cell

> immunity seen in some

> chronic infections that are eventually controlled

> and eliminated, and

> the ability of some persistent tumors to provide

> protection from a

> secondary tumor challenge if the original tumor is

> not removed.

>

> " Giving T cells a rest by terminating exposure to

> viral antigen

> simulation following the acute phase of infection

> seems to be

> necessary if T cells are to differentiate into

> long-term

> antigen-independent memory T cells, " Dr. Ahmed says.

> " Therapeutic

> vaccine approaches that provide antigen

> re-stimulation during

> persistent infections may not allow the ability for

> memory T-cell

> proliferation. However, antiviral therapy or cancer

> chemotherapy may

> provide rest from antigen stimulation and allow

> partial recovery of

> some memory T cell functions. By combining drug

> treatment with

> therapeutic vaccination or cytokine therapies we may

> be able to

> prevent loss of T cell memory and establish

> long-term protective

> immunity. "

>

> Contact: Holly Korschun

> hkorsch@...

> 404-727-3990

> Emory University Health Sciences Center

>

> For more information on meningitis click here.

>

>

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