Understanding innate immunity may provide insight into treatment of HIV

Further study of innate elite controllers of HIV may lead to the development of more effective treatment or prevention methods, including a vaccine, according to a speaker at the 14th International Congress on Infectious Diseases in Miami.

“We do not know what immunological correlates are at work in these elite controllers yet,” Galit Alter, PhD,assistant professor of medicine in the division of AIDS research at Massachusetts General Hospital, said during a presentation. “But we would like to further observe the ability to spontaneously lyse tumor targets before T-cells are even induced early in the infection process.”

Data suggest that certain major histocompatibility complex class-1 alleles may be enriched in patients who maintain undetectable viral loads in the absence of antiretroviral therapy, according to Alter.

These molecules interact with T-cell receptors found on cytotoxic CD8 cells and innate immune receptors, including the “killer immunoglobulin-like” receptors, which are found on the surface of innate cytotoxic “natural killer” cells, she said.

“It is plausible that these natural killer cells may play a central role in control of the HIV virus,” Alter said. “The cells expand rapidly following acute infection, and specific populations of killer immunoglobulin-like receptors and natural killer cells expand preferentially in patients that co-express protective killer immunoglobulin-like and major histocompatibility class-1 combinations.”

This combination and expansion may be linked to containment of HIV replication in vitro. Despite this early expansion of natural killer cells in the periphery, these cells do not gain access to secondary lymphoid organs, according to Alter. This allows the virus to replicate, even in cases of early suppression.

“These data suggest that durable control of HIV infection is associated with an early aggressive deployment of highly licensed antiviral natural killer cells in the periphery that may provide specific and nonspecific control of HIV viral replication in acute infection,” she said. “At the same time, large quantities of cytokines and chemokines required for the induction of high-quality adaptive immune responses may be produced. This, in turn, may allow these elite controllers to maintain control of HIV replication most likely in contained tissue sites.”

Alter said it may be possible for a vaccine to recruit these cells to control the virus early in the infection stage.

“It may also be possible to use this information in serodiscordant couples,” she said. “It may be feasible to take plasma samples from serodiscordant couples to find other antibodies.”– by Rob Volansky

For more information:

Alter G. #17.001. Presented at: 14th International Congress on Infectious Diseases; March 9-12, 2010; Miami.