Has poor CD4 T cell reconstitution in the gut been exaggerated?

In recent years, loss of CD4 T cells from the gut of HIV-positive people has become a major research focus.

Gut CD4 T cell depletion happens rapidly after infection, and many studies have suggested that recovery of these cells is typically limited even after prolonged antiretroviral therapy (ART). However, the bleakest data has been obtained by measuring the percentage of CD4 T cells in the gut relative to other lymphocytes, and this can produce misleading results because CD8 T cell numbers are increased in the setting of HIV infection.

A new paper from Irini Sereti’s laboratory at NIAID reports that the picture is far more encouraging when absolute numbers of CD4 T cells are measured. Taking samples from both the colon and terminal ileum, the researchers show that absolute CD4 T cell numbers among people on long-term (>5 years) ART with viral loads less than 50 copies are comparable to uninfected controls. The numbers are expressed as CD4 T cells per gram of tissue and the results for the ART-treated vs. control group were as follows: 3.9×10⁶ vs. 3.6×10⁶ (colon) and 1.0×10⁶ vs. 1.6×10⁶ (terminal ileum). The researchers note that in some prior papers, “the persistence of a high proportion of CD8 T cells in HIV-infected patients appeared to result in an underestimation of CD4 T cell reconstitution…our findings are in agreement with recent studies using both immunohistochemistry and flow cytometric analyses; some of these have suggested that gut CD4 T-cell reconstitution may even exceed what occurs in peripheral blood.”

The researchers also write: “It has also been proposed that initiating ART therapy during acute infection may result in more rapid and complete reconstitution of the CD4 T-cell population in the gut. Three of the four patients in this study who reconstituted their CD4 T-cell counts in the colon to values higher than the median of the HIV-uninfected group had peripheral nadir CD4+ T-cell counts of less than 250 cells per microliter. This suggests that CD4 T-cell restoration may occur despite substantial disease progression before ART initiation.”

Ref: Ciccone EJ et al. Cycling of gut mucosal CD4+ T cells decreases after prolonged anti-retroviral therapy and is associated with plasma LPS levels. Mucosal Immunology (2010) 3, 172–181; doi:10.1038/mi.2009.129; published online 2 December 2009
http://www.nature.com/mi/journal/v3/n2/abs/mi2009129a.html