Aging is associated with a complex remodeling of the immune system. While adaptive immune responses show impairment with aging, innate immune responses tend to improve it.

Low numbers of CD3+, CD4+ and CD8 T cells have been observed in aged individuals. B lymphocytes tend to diminish as well. However, an increase in NK cells and effector T lymphocytes (CD28- CD8) can be shown.

Effector T lymphocytes are characterized by:

1. expression of markers of cytotoxicity;
2. high levels of NK activity;
3. expression of the same inhibitory receptors as NK cells;
4. no cytokine production.

For effector T lymphocyte-mediated cytotoxicity of virus-infected cells to occur, viral epitopes need to be exposed on the cell surface in the absence of MHC class I molecule expression, just as it has been shown with NK cells. Indeed, chronic infection with intracellular parasites is known to hinder MHC class I expression on cell surface.

In elderly patients with chronic hepatitis C, infected hepatocytes can be shown to express a wide variety of HCV antigens, reflecting latency or active replication, as opposed to low or absent MHC class I expression. This favors elimination of infected hepatocytes by NK cells and effector T lymphocytes.

A negative correlation has been observed between outcome of hepatitis and patients' age. Liver biopsies from elderly patients generally show chronic active hepatitis or cirrhosis, which are far less commonly observed in young patients or young adults. Overproduction of proinflammatory cytokines, namely TNF-alpha, IL-1 and IL-6, is responsible for enhanced immuno-phlogosis and underlies a more extensive damage to liver parenchyma.

Since interferon-alpha has been shown to upregulate MHC class I molecule expression on infected hepatocytes, it may turn useful as a tool to inhibit NK cell- and effector T lymphocyte-mediated cytotoxicity. Thus, a rationale exists to recommend interferon-a administration in hepatitis C patients, especially in elderly patients.

Keywords: proinflammatory cytokines, immune system, MHC class I expression