Research ArticlesHIV

HIV-Specific Cytolytic CD4 T Cell Responses During Acute HIV Infection Predict Disease Outcome

Science Translational Medicine  29 Feb 2012:
Vol. 4, Issue 123, pp. 123ra25
DOI: 10.1126/scitranslmed.3003165

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T Cells Take Center Stage

With more than 33 million infected people worldwide, the HIV/AIDS pandemic is the most devastating infectious disease in recent history. The virus infects and kills one of the central players in the immune system—the CD4 T cell. CD4 T cells provide critical helper signals to B lymphocytes, enabling B cells to produce antibodies, and they also aid another key immune cell, CD8 T cells, which kill virally infected cells. However, CD4 T cells specific for HIV are preferentially infected with this deadly virus and therefore are presumed to be unable to help the host immune system combat HIV.

Given the importance of CD4 T cell responses in other viral infections, Soghoian et al. sought to revisit the role of HIV-specific CD4 T cells in the control of HIV infection. They followed a group of HIV-positive patients starting almost immediately after the individuals became infected. The patients who were able to better control HIV showed a robust and early expansion of their HIV-specific CD4 T cells compared to those subjects who were not able to control the virus. Surprisingly, these T cells comprised not only classical CD4 helper cells but also cytolytic “killer” CD4 T cells. Indeed, these CD4 T cells were able to kill HIV-infected cells directly, suggesting that they are involved in the control of HIV.

The researchers also made another key observation. At the earliest point during the acute phase of HIV infection, they found that patients who had HIV-specific CD4 T cells containing lots of the death protein granzyme A progressed much more slowly (1 year or more) to full-blown disease than did those patients with T cells containing much less granzyme A. The quality of T cell response in acute HIV infection was able to predict better or worse disease outcomes later on. The unexpected expansion of CD4 T cells with the ability to directly kill HIV-infected cells observed in this study not only demonstrates the key role that cytolytic CD4 T cells play during HIV infection but also sheds new light on the general immunobiology of these cells and raises questions about their roles in other viral infections.