Rapid ageing of T-cells after HIV infection could help explain cancers, diseases of ageing

HIV infection can cause a specific sub-group of CD4 T-cells to age by as much as 20 or 30 years within three years of contracting the virus, American researchers report. This ageing process could help to explain the unusual rate of diseases associated with the elderly in HIV-infected people in their middle years, they speculate.

Cancers, cardiovascular disease and bone thinning (osteoporosis) have been observed either at high rates or at younger ages in people with HIV infection, leading to speculation that HIV infection and the inflammation associated with prolonged activation of the immune system by the virus may be the cause of the early onset of diseases of ageing in HIV-positive people.

Many of the conditions associated with ageing are influenced by the loss of immune function with age.

Some researchers have become interested in determining whether HIV has direct effects on the immune system that speed up the ageing process, effectively leaving a person with HIV infection with the immune system of a much older person.

T-cell ageing can be measured by looking at the ends of chromosomes within the cells. The ends of chromosomes are protected by telomeres, which stop them from being damaged or fusing together. As we age, the telomeres become shorter. Eventually the telomeres become so short that the cell ceases to function properly.

The study reported this week in the journal PLoS One, conducted by UCLA AIDS Institute, shows that among people infected with HIV, two subsets of naïve CD4+ T cells show signs of telomere shortening equivalent to 20 to 30 years of ageing within two to three years of infection.

A similar rate of ageing happened in younger (20-39) and older (39-58) adults.

Patients also experienced a decline in the number of naïve CD4+ cells in comparison to age-matched controls, even though this group of CD4+ cells is not the primary target of HIV infection, nor the primary sub-group depleted as a result of HIV infection. Indeed, this subset was more depleted than any other subset of CD4+ cells.

Naïve CD4+ T-cells are needed to respond to new infections. As we age, they become less plentiful, making it more difficult for the immune systems of older people to respond to new infections they haven’t encountered before. These cells are also needed to develop immunity after vaccination, which is why elderly people are less likely to develop protection after vaccination than younger people.

In adults with HIV aged 20-39 the naïve cell subset was 2.9 times smaller than in age-matched HIV-negative controls (p=0.0007). The difference in this subset was not significant in those aged 39 to 58.

What’s more, the naïve T cell subset being studied (CD31^- CD4⁺) is not restored to normal levels for a person’s age after they start antiretroviral treatment. Looking at a separate sample of patients from the Multicenter AIDS Cohort Study, the researchers found that this subset of CD4+ cells remained significantly smaller in HIV-positive people two years after starting antiretroviral treatment.

The researchers speculate that the increased rate of some cancers seen in people with HIV when compared to age-matched controls, as well as a higher rate of some infections, may be due to the immune defects detected by this study.

The researchers also suggest that accelerated HIV disease progression in the over-50s could be a consequence of the additive effects of HIV infection and of ageing on this CD4+ T-cell subset.

"Our findings have important implications for the health of both young and old HIV-1–infected adults," said lead investigator Tammy M. Rickabaugh, an assistant research immunologist in the division of hematology and oncology at the David Geffen School of Medicine at UCLA. "They underscore the importance of developing new approaches to boost immune function to complement current treatments, which are exclusively directed against the virus."

Rickabaugh TM et al. The dual impact of HIV-1 infection and aging on naïve CD4+ T-cells: additive and distinct patterns of impairment. PLoS One 6 (1): e16459, 2011. doi:10.1371/journal.pone.0016459 (Download full text article here).