Attack of the killer helpers (part two)

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). [1]

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. [2]

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. [3]

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).


  1. Killer helpers. Basic Science Blog (June 2009).
  2. 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.
  3. 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.

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