1147. Antigen-Specific IFN-γ Responses Decreases as Peripheral Blood Regulatory T Cell Proportion Rises During Cutaneous Leishmaniasis Treatment
Session: Poster Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011
Room: Poster Hall B1
Handouts
  • IDSA 2011.pdf (376.1 kB)
  • Background: 

    Cutaneous leishmaniasis (CL) remains an important public health problem in Latin America. Antigen-specific-Th1-responses are crucial for parasite control. Regulatory T cells (Tregs) are capable of suppressing T cell responses limiting parasite clearance. We previously demonstrated an increased proportion of Tregs at the infection site and a diminished proportion of peripheral blood Tregs, suggesting an active migration into infected tissue. In addition, Tregs normalized after standardized treatment, suggesting that the homing process is resolved. We hypothesized that antigen-specific-IFN-γ responses decrease as Tregs proportion increase during standardized treatment.  

    Methods: 

    At our center in Lima, we enrolled 20 CL patients. Blood samples were drawn prior to standardized treatment on day 0, and at days 10 and 20 during treatment. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation from heparinized blood samples and cultured with soluble Leishmania antigen for 48 hours. Supernatants were collected and IFN-γ concentration measured by EIA.

    Results: 

    We found that prior to treatment initiation the median antigen-specific IFN-γ production was 2787 pg/mL (IQR: 196.5-5590). In addition there was a trend for decreased IFN-γ responses during treatment (Day 10 median: 2206 pg/ml IQR: 921- 5252, Day 20 median: 626.5 pg/ml, IQR: 372.5-1768, Wilcoxon test Day 0 vs. Day 20 p=0.095). 

    Conclusion:

    During cutaneous leishmaniasis, Tregs actively migrate to the infection site. After standardized treatment, the homing process is resolved and the Tregs redistribute to the blood. Here we show that as Tregs proportion increases, the antigen-specific-IFN-γ production decreases, suggesting that these Tregs are actively suppressing the effector responses. Since an important proportion of this Tregs are recently redistributed from the infection site, we suggest that Tregs are blunting effector responses to Leishmania at the infection site. Our study highlights the role of Tregs in modulating the immune response during cutaneous leishmaniasis.


    Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

    Fernando Woll, MD1, Nicolas Barros, MD2, Aldo De Ferrari, Medical Student3, Luis C. Watanabe, MD2, Alejandro Llanos-Cuentas, MD PhD3, A. Clinton White, MD, FIDSA4 and Martin Montes, MD5,6, (1)Immunology, Universidad Peruana Cayetano Heredia, Lima, Peru, (2)Universidad Peruana Cayetano Heredia, Lima, Peru, (3)Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru, (4)The Paul R. Stalnaker, MD Distinguished Professor, University of Texas Medical Branch, Galveston, TX, (5)Medicine/Infectious Diseases, University of Texas Medical Branch, Galveston, TX, (6)Pathology/Immunology, Universidad Peruana Cayetano Heredia, Lima, Peru

    Disclosures:

    F. Woll, None

    N. Barros, None

    A. De Ferrari, None

    L. C. Watanabe, None

    A. Llanos-Cuentas, None

    A. C. White, None

    M. Montes, None

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.