Cytolytic Cell Expression Predicts HIV Prognosis

The role of HIV-specific cluster of differentiation 4 (CD4) thymocyte (T) cell responses in the control of viral replication after acute infection is unknown, but may have the capacity to directly recognize and kill virally infected cells.

To investigate whether CD4 T cell responses are important in the early control of HIV infection, a team at the Ragon Institute (Charlestown, MA, USA) conducted a longitudinal cohort study enrolling a group of 11 volunteers who were in the earliest stages of HIV infection, a time when viral levels are exceedingly 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. The HIV-specific CD4 T cell responses showed activity associated with cell killing and could even destroy HIV-infected macrophages, which is an unusual function for CD4 T cells, which have traditionally been seen as helper cells.

In addition, the scientists 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. A larger group of HIV-infected individuals were examined and it found that those with higher levels of granzyme A in their HIV-specific CD4 T cell response immediately after infection progressed more slowly to acquired immunodeficiency syndrome (AIDS) and did not require antiretroviral therapy as quickly as did those with lower levels of the protein.

The authors concluded that the association of granzyme A expression with a more effective HIV-specific CD4 cell response suggests that measuring levels of the protein may allow prediction of disease outcome at the earliest stages of infection, something which is not currently possible. Hendrik Streeck, MD, PhD, a senior author of the study said, "We observed the emergence of CD4 T cells able to kill HIV-infected cells in those patients who are able to control viral replication soon after acute infection. These cells appear very early in HIV infection, and we believe they may set the stage for the course of the disease." The study was published on February 29, 2012, in the journal Science Translational Medicine.

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Ragon Institute