© 2007 American Thoracic Society
Another Round for the CD4+CD25+ Regulatory T Cells in Patients with TuberculosisTo the Editor:We read with interest the recent article by Guyot-Revol and colleagues (1) and the letter to the editor by Gazzola and colleagues commenting on the article (2). Guyot-Revol and colleagues found that regulatory lymphocytes (Treg cells) were expanded in patients with active tuberculosis (TB) from a nonendemic setting and may play a role in suppression of type 1 immune responses. In their comments, Gazzola and colleagues (2) highlighted the significance of accurate approaches to evaluate the frequency and level of FoxP3 expression at the single cell level. Treg cells are considered among the most informative criteria of current immune status, controlling homeostasis and immunopathology (3). We agree with Gazzola and colleagues, since the functional properties of these cells should be analyzed at the single cell level. We also realize that differences may exist in distinct clinical and temporal forms of TB (1). Therefore, studies focused on describing the frequencies of Treg cells, not only in patients with active TB (1) but also following the specific treatment in Mycobacterium tuberculosis (Mtb) drug-sensitive and multidrug-resistant (MDR) patients from tropical countries, are needed to better characterize successful therapy and management. Based on this, we realize that T-cell–mediated suppression might be responsible for the low level of chronic infection seen with many pathogens, and we hypothesize that Treg cells may play a role in latency as well. Since Treg cells control inflammatory reactions, their activation and function during these processes might be mediated directly by bacterial products as well, such as the specific Mtb ESAT-6 (M. tuberculosis 6 kD–early secreted antigenic target) antigen (4). At this time, little is known about the profile of Treg cells in patients with TB from endemic settings. If Treg cells can be expanded in the site of infection during active TB, those cells would be able to decrease the immune response against Mtb (1). Alternatively, Treg cells from patients with TB under/after specific treatment may be able to control inflammatory processes affecting outcome from the disease. Our cross-sectional data strongly support the latter. When the in vitro CD4+CD25+high Treg phenotype was studied using ESAT-6 in 20 successfully treated patients with TB, a significant (mean ± SEM 3.68% ± 1.11; p < 0.01) enhanced profile was detected, compared with active (1.47% ± 0.26; n = 8) and MDR (0.95% ± 0.32; n = 7) patients with TB, as well as contact individuals (0.08% ± 0.01; n = 6) and healthy donors (0.98% ± 0.27; n = 8) in a coendemic area for TB and leprosy in Brazil. Consistent with results from Roncador and colleagues (5), the FoxP3 intracellular detection at the single cell level supports previous findings (see Figure 1). Our data not only support previously reported results (2) but also add supplementary information regarding patients with TB who are successfully treated or failing chemotherapy. Other follow-up studies are warranted to better clarify this important issue.
Vanderbilt University Medical Center, Nashville, Tennessee and Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil
Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil Acknowledgments The authors thank Drs. Marilza Ribeiro-Carvalho (FIOCRUZ, Rio de Janeiro, Brazil), Andreia Fortes, and Margareth Dalcolmo (Reference Center for Tuberculosis, Rio de Janeiro, Brazil) for their helpful discussion, and Dr. Audrey Kinter (NIAID, NIH, Bethesda, MD) for providing the FoxP3 staining kit and use of the lab facility. 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
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