CD4 T-cell responses to commensal bacteria in the gut

Richard Jefferys, TAG

There has been a lot of attention given recently to the role of gut CD4 T cell depletion in HIV pathogenesis. Surprisingly, very little is known about which antigens are targeted by gut CD4 T cells; at least one study has reported evidence of memory CD4 T cell responses to candida albicans (the fungus that causes thrush) but an absence of the typical memory responses against opportunistic pathogens (also called “recall responses”) found in the blood. [1]

More recently, gut HIV-specific CD4 T cell responses have been detected some elite controllers [2] and in HIV-infected individuals showing robust CD4 T cell recovery in the gut on antiretroviral therapy (this latter data was presented at CROI by Satya Dandekar. [3] Studies in mice have suggested that there are likely be CD4 T cell responses to commensal bacteria in the gut, but there is little research addressing this question in humans. In a new paper in press at Clinical Immunology, Rawleigh Howe and colleagues from Cara Wilson’s group at the University of Colorado describe their initial efforts to fill this knowledge gap. [4]

Using flow cytometric techniques, the researchers were able to detect the presence of CD4 T cells making interferon gamma in response to stimulation with several gut commensal bacteria species (Enterobacter, E. coli, Enterococcus species) as well as to the pathogen, Salmonella typhimurium. CD4 T cells making IL-17 – Th17 cells – were also detected but at a much lower frequency. Bacteria-specific CD4 T cell responses could also be detected in the blood but at significantly lower levels; the difference in magnitude between gut and blood ranged from 8.5 to 19.5 fold. When responses to all four bacterial antigens were summed, the median frequency of interferon gamma-producing CD4 T cells was 0.24% in the gut compared to 0.02% in blood.

The researchers suggest that the CD4 T cell responses revealed in this study play a role in containing bacteria in the gut under normal conditions. Such a role would be consistent with recent studies indicating that T cell depletion can lead to systemic dissemination of gut bacteria (microbial translocation). Another implication of the data is that people with HIV infection may have altered CD4 T cell reactivity to commensal bacteria, and Cara Wilson’s group is addressing this possibility in ongoing studies.

TAG Basic Science Weblog. (23 Feb 2009)


  2. vaccin/2009/01/muco.html
  3. =10652
  4. Howe R et al. Evidence for dendritic cell-dependent CD4+ T helper-1 type responses to commensal bacteria in normal human intestinal lamina propria. Clinical Immunology. doi:10.1016/j.clim.2008.12.003. Article in press.

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