Attack of the killer helpers (part two)
1 February 2013. Related: Basic science.
Richard Jefferys, TAG
Among the many tasks of the immune system, the responsibility for recognising 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 it was not highlighted 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.
TAG Basic Science Blog. Attack of the killer helpers (part two). (27 November 2012).
- Killer helpers. Basic Science Blog (June 2009).
- Burwitz BJ et al. Retrovirology. 2012 Nov 6;9:91. doi: 10.1186/1742-4690-9-91. CD8+ and CD4+ cytotoxic T cell escape mutations precede breakthrough SIVmac239 viremia in an elite controller. Retrovirology. 2012 Nov 6;9:91. doi: 10.1186/1742-4690-9-91.
- Soghoian DZ et al. HIV-specific cytolytic CD4 T cell responses during acute HIV infection predict disease outcome. Sci Transl Med. 2012 Feb 29;4(123):123ra25. doi: 10.1126/scitranslmed.3003165.