This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lalvani, A. Articles by Guyot-Revol, V. Search for Related Content PubMed Articles by Lalvani, A. Articles by Guyot-Revol, V.

FoxP3 mRNA Expression in Regulatory T Cells from Patients with Tuberculosis

We thank Gazzola and colleagues for their interest in our recent article, the first to describe a role for regulatory T cells (Tregs) in tuberculosis (1). Our main finding was an increased percentage of CD4+CD25^high T cells in the CD4+ T-cell fraction of peripheral blood mononuclear cells (PBMCs), and increased FoxP3 mRNA expression in PBMCs in patients with tuberculosis compared with healthy control subjects. In contrast, Gazzola and coworkers' interim results from their ongoing study (as mentioned in their letter) show no increase in CD4+CD25^high T cells in patients with tuberculosis compared with healthy control subjects, and they seem not to have measured FoxP3 expression in PBMCs. The median proportion of CD4+CD25^high T cells in their healthy controls (1.9%) was not dissimilar to ours (1.17%), suggesting that our gating was comparable.

When we compared FoxP3 mRNA expression in CD4+CD25+ T cells in patients and controls, we found no significant difference, suggesting that the increased FoxP3 expression in tuberculosis reflects increased frequencies of Tregs rather than increased expression of FoxP3 per cell. Gazzola and coworkers compared FoxP3 expression in CD4+CD25^high T cells and found a 24-fold increase in patients with tuberculosis. In general, CD4+CD25+ T cells constitute about 5–10% of CD4+ T cells, whereas CD4+CD25^high T cells constitute about 1–2%. Therefore, if CD4+CD25^high T cells in our patients with tuberculosis were expressing 24 times more FoxP3 than in our controls, we should have observed an approximate four- or fivefold increase in FoxP3 expression in the CD4+CD25+ T-cell fraction, 20% of which was composed of CD4+CD25^high T cells. The fact that we did not see such a difference is at variance with Gazzola and coworkers' observation. Thus, two of Gazzola and coworkers' findings are in contrast to our own for unclear reasons. However, we are not told the size or the clinical and demographic characteristics of their study population (e.g., HIV coinfection status), all of which are factors that might shed light on the differing results.

We agree that it is helpful to measure FoxP3 expression in the CD4+CD25^high T-cell fraction, as Gazzola and coworkers have done. We also agree that it is desirable to assess FoxP3 expression at the single cell level, but we do not believe this is "mandatory"; indeed, Gazzola and coworkers do not appear to have done this themselves. Notwithstanding, the availability of anti-FoxP3 monoclonal antibodies (2), which allow convenient detection of intracellular FoxP3 expression in individual CD4+CD25^high T cells, will further advance this interesting field in the near future.

Ajit Lalvani and Valerie Guyot-Revol

Tuberculosis Immunology Group, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom

FOOTNOTES

Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

1. Guyot-Revol V, Innes JA, Hackforth S, Hinks T, Lalvani A. Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. Am J Respir Crit Care Med 2006;173:803–810.[Abstract/Free Full Text]
2. Roncador G, Brown PJ, Maestre L, Hue S, Martinez-Torrecuadrada JL, Ling KL, Pratap S, Toms C, Fox BC, Cerundolo V, et al. Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell level. Eur J Immunol 2005;35:1681–1691.[CrossRef][Medline]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lalvani, A. Articles by Guyot-Revol, V. Search for Related Content PubMed Articles by Lalvani, A. Articles by Guyot-Revol, V.