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. 
More recently, gut HIV-specific CD4 T cell responses have been detected some elite controllers  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.  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 Wilsons group at the University of Colorado describe their initial efforts to fill this knowledge gap. 
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 Wilsons group is addressing this possibility in ongoing studies.
TAG Basic Science Weblog. (23 Feb 2009)
- http://tagbasicscienceproject.typepad.com/tags_basic_science_ vaccin/2009/01/muco.html
- http://app2.capitalreach.com/esp1204/servlet/tc?c=10164&cn=retro&e=10652&m=1&s=20415&&espmt=2&mp3file=10652&m4bfile =10652
- 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.