Attack of the Killer Helpers (Part Two)

Among the many tasks of the immune system, the responsibility for recognizing and killing virus-infected cells largely falls to the subset of CD8 T cells designated cytotoxic T-lymphocytes (CTL). The question of whether CD4 T cells (traditionally called just "helper" cells) can exert cytotoxic functions has historically been controversial, but over the past decade studies have convincingly documented the existence of cytotoxic CD4 T cell responses in a variety of different settings, including HIV and SIV infection (as previously covered on this blog). A new paper in the open-access journal Retrovirology from Jonah Sacha's research group at Oregon Health and Science University now reports that not only are cytotoxic CD4 T cell responses detectable in macaques controlling a pathogenic SIV isolate, but they can drive the selection of immune escape mutations. As the authors note, this represents compelling evidence that CD4 T cells can directly suppress viral replication.

Although I neglected to highlight it on the blog at the time of publication, a human study from the laboratory of Hendrick Streeck also argues for a key role of cytotoxic CD4 T cell responses in controlling HIV. Published in Science Translational Medicine back in February of this year, the study showed that HIV-specific cytotoxic CD4 T cell activity predicted superior control of viral load and slower disease progression (as assessed by time to CD4 T cell count <350, time to ART initiation or time to viral load >100,000 copies) in a cohort of acutely HIV-infected individuals.

Taken together, these results further underscore the importance of considering virus-specific CD4 T cell responses, both in studies of natural control of HIV replication and in attempts to design effective immune-based therapies.

Richard Jefferys is the coordinator of the Michael Palm HIV Basic Science, Vaccines & Prevention Project Weblog at the Treatment Action Group (TAG). The original blog post may be viewed here.