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Ragon Institute study finds HIV-specific CD4 cells that control viral levels
Date:2/29/2012

gly high. A year into the study, participants were divided into two groups based on the level of HIV in their bodies one group was able to keep HIV at low levels while the other group apparently had no immune control over HIV replication. Retrospective analysis of samples taken throughout the year showed striking differences in the CD4 T cell responses in both groups. While the HIV-specific CD4 responses in the group that did not control HIV replication quickly dropped and stayed low, the same response increased significantly in participants able to effectively control the virus, suggesting a role for HIV-specific CD4 cells in viral control.

Additional experiments revealed that the HIV-specific CD4 T cell responses showed activity associated with cell-killing and could even destroy HIV-infected macrophages an unusual function for CD4 T cells, which have traditionally been seen as helper cells. In addition, the researchers determined that the presence of a specific cell-death protein called granzyme A prominently distinguished HIV-specific CD4 cells of participants maintaining a lower "viral set point" from those less able to control viral levels.

To validate these findings, the researchers examined a larger group of HIV-infected individuals and found that those with higher levels of granzyme A in their HIV-specific CD4 T cell response immediately after infection progressed more slowly to AIDS and did not require antiretroviral therapy as quickly as did those with lower levels of the protein. "The key baseline difference between these two groups has to do with the quality, not the quantity, of the HIV-specific CD4 T cell response," explains Streeck, an assistant professor of Medicine at Harvard Medical School. "In those who progressed to a lower viral set point, the early CD4 response was dominated by granzyme A expression, which was highly predictive of the rate of disease progression."

Associating a particular CD4 T cell activity with
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Contact: Sarah Dionne
smdionne@partners.org
617-726-6126
Massachusetts General Hospital
Source:Eurekalert

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