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T-cell senescence linked to KS in peoplewith good HIV control

1 December 2010. Related: Conference reports, Cancer and HIV, Basic science and immunology, .

Mark Mascolini, natap.org

HIV-positive people with Kaposi sarcoma (KS) despite tight control of HIV replication had higher levels of immunosenescent (immunologically feeble) CD4 and CD8 cells than HIV-positive people without KS, according to results of a comparative study at the University of California, San Francisco (UCSF). [1] People with KS also had lower levels of naive CD4 and CD8 cells.

Accelerated senescence of critical immune system cells, including CD4s and CD8s, has been documented in people with HIV infection, despite good response to antiretroviral therapy. Researchers postulate that ongoing immune cell activation and turnover account for this immune-cell exhaustion. Until this study, however, T-cell senescence had not been compared in HIV-infected people with versus without an AIDS malignancy, in this case KS.

Researchers at the University of California, San Francisco (UCSF) reported earlier on a group of HIV-infected men with KS despite high CD4 counts and low viral loads. [2]

When KS first emerged as an AIDS-defining condition, it appeared mostly in people with low CD4 counts. Because the men in this study were responding well to antiretroviral therapy, the UCSF team wondered whether KS may be a marker of immunosenescence in the current antiretroviral era.

To find out, the researchers compared immune-cell marker levels in 19 people with unremitting KS despite good control of HIV replication and 47 HIV-positive people without KS. The investigators considered T cells with CD57 receptors (CD57+) or without CD28 receptors (CD28-) as immunosenescent cells. They defined naive T cells as those bearing CD27, CD28, and CD45RA receptors (CD27+CD28+CD45RA+).

The 19 people with biopsy-proved KS were older than the no-KS group (median 54 versus 43 years, p<0.001). Compared with the no-KS group, people with KS had lower CD8 counts (median 933 versus 1200) but higher CD4 counts (median 701 versus 523), though these differences lacked statistical significance. Everyone in both groups had a CD4 count above 300 and a viral load below 75 for at least 24 months. The study excluded people taking interferon for hepatitis C virus, current malignancy (other than KS), or a history of immunomodulatory therapy. There were no women in either group.

People with KS had a significantly higher proportion of CD57+ CD8 cells (median 41.5% versus 27.7% in controls without KS, p=0.005 in an age-adjusted analysis). The researchers also saw a trend toward higher frequency of CD57+ CD4 cells in patients with KS (median 7.4% versus 3.7%, age-adjusted p=0.07).

KS patients had a higher proportion of CD28- CD4 cells than people without KS (median 9.1% versus 4.8%, age-adjusted p=0.03). And people with KS had a higher proportion of CD28- CD8 cells (median 60.5% versus 51.3%, age-adjusted p=0.044).

Naive (CD27+CD28+CD45RA+) CD8-cell proportions were lower in people with KS than in those without KS (median 11.3% versus 20.7%, age-adjusted p=0.022). And there was a trend toward lower frequency of naive CD4 cells in the KS group (median 23.0% versus 32.2%, age-adjusted p=0.11).

Telomere length did not differ between the people with versus without KS. (Telomeres are the end regions of human DNA that protect the chromosome from deterioration. Telomere shortening in humans can induce replicative senescence and block cell division.)

The UCSF team suggested that elevated populations of immunosenescent T cells and a shallow naive T-cell pool provide “strong evidence that immunosenescence is associated with presence of KS in these individuals, in spite of their undetectable viral loads and relatively high CD4 counts.” What the study does not explain, workshop cochair Charles Flexner observed, is how much HIV versus KSHV (the herpesvirus that causes KS) may be driving immunosenescence.

References:

  1. Unemori P, Leslie KSL, Hunt PH, et al. T-cell immunosenescence is associated with the presence of Kaposi’s sarcoma in antiretroviral treated human immunodeficiency virus infected persons. 1st International Workshop on HIV and Aging. 4-5 October 2010. Baltimore. Abstract O_02.
  2. Maurer T, Ponte M, Leslie K. HIV-associated Kaposi’s sarcoma with a high CD4 count and a low viral load. N Engl J Med. 2007;357:1352-1353. http://www.nejm.org/doi/full/10.1056/NEJMc070508

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