The lifelong immunity to viral infection involves a multistep process:
• The maintenance of so-called long-lived memory lymphocytes – lymphocytes are circulating white blood cells that play a critical role in the immune response
• Upon reinfection, these memory lymphocytes then generate large numbers of short-lived cells that actively combat infection
• Lastly, the pool of long-lived memory cells is replenished for use in future assaults.
There are a number of viral infections in which the virus following active infection can become quiescent and actually be incorporated in the host DNA and subsequently be reactivated under the appropriate conditions. An example of a low-level virus of this type is cytomegalovirus (CMV) – a herpes virus that can reside within a host for a lifetime. To combat such an infection, a balance is achieved between the maintenance of a pool of long-lived immunological memory cells and short-lived lymphocytes designed to fight the infection as described above. A balance of these modalities confers lifelong immunity to the individual.
The issue becomes more problematic in the case of persistent infections with high viral loads such as the human immunodeficiency virus (HIV) that causes AIDS. In such infections, the ability to maintain a consistent pool of long-term memory cells can be compromised on account of the necessity to maintain a persistently high level of short-term lymphocytes. In the case of AIDS it is believed that a constantly elevated population of CD8+ lymphocytes (CD8 is a particular protein that resides on the cell surface of these cells) that are involved in combatting the HIV infections leads to a decreased pool of memory cells and eventually results in the collapse of immunity towards HIV.
What is not clear is the actual mechanism that is responsible for this immunological imbalance in regard to chronic viral infections. In attempt to elucidate this issue, Dr. Michael A. Paley and his colleagues at the Department of Microbiology and Institute for Immunology at the Perelman School of Medicine at the University of Pennsylvania worked with chronically infected mice as the animal model for their studies. From their work, they discovered two unique subsets of CD8+ lymphocytes in response to chronic viral infection – one subset involved in the renewal of the CD8+ population and the other in differentiation. Furthermore, they found that elimination of either of these subsets resulted in the organism’s inability to control chronic infection. These findings seem to suggest that an imbalance in differentiation and renewal may be ultimately responsible for the collapse of immunity in human patients suffering from chronic infection.
The clarification of this mechanism may help in the ultimate development of targeted therapies for chronic viral infections in humans.