European Society of Mycobacteriology - Instituto Nacional de Saúde ...

OP-18
MYCOLIC ACID-INDUCED IFN-γ PRODUCTION BY
CD1-RESTRICTED T CELLS FROM TUBERCULOUS PATIENTS
Rodríguez-Güell, E 1 , Alonso, C 2 , del Val-Romero, B 2 , Clivillé, R 2 , Secanella,SP 1, Roura-Mir,C 3 , Cañete, C 4 , Navarro, A 4 ,
de Gispert, FX 4 , Luquin, M 1 , Julián,E 1
1. Dept. Genètica i Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra (Barcelona)
2. Dept. Microbiologia, Consorci Sanitari Integral, L’Hospitalet de Llobregat (Barcelona)
3. Dept. Fisiologia i Immunologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra (Barcelona)
4. Unitat de Respiratori, Consorci Sanitari Integral, L’Hospitalet de Llobregat (Barcelona)
Introduction
The cell wall of Mycobacterium tuberculosis (MTB) has a large number of structurally diverse lipids. Mycolic acids (MAs) merit
special interest because their immunogenicity has been demonstrated in CD1-restricted T cell clones; specifically, they are
presented by CD1b molecules. To date, the recognition of MAs in tuberculous patients (TB) has not been studied.
The purpose of the study was to determine whether MAs are recognized by the immune system of TB patients and,
in the event of this being so, to study the evolution of this response throughout anti-TB treatment.
Methods
Immature dendritic cells (iDCs) isolated from 31 TB patients at the time of diagnosis and throughout anti-TB treatment,
20 PPD-positive and 20 PPD-negative donors were analysed by cytometry for CD1b surface expression. Subsequently,
the samples were irradiated and cultured with autologous lymphocytes in the presence of phytohemaglutinin, MTB and
purified MAs as stimuli. After 48 hours, IL-10 and IFN-γ were quantified by enzyme-linked immunosorbent assay.
Results
No significant differences among the surface expression of CD1b in iDCs from healthy donors or TB patients were observed
at any time during the disease. iDCs from all the individuals were therefore able to present MAs.
Median levels of stimuli-induced IL-10 in samples obtained at the outset of anti-TB treatment were lower than those
obtained at the end; however, no significant differences were observed. Nor were any differences observed among the
IL-10 levels obtained from the different groups of individuals.
In TB patients, MA-induced IFN-γ median values obtained at the end of prophylaxis were significantly higher, statistically,
than those elicited at the beginning. Grouping the samples of the 31 TB patients in terms of collection time, IFN-γ median
levels followed an upward trend throughout anti-TB treatment, reaching maximum levels at the point of disease cure.
Furthermore, in PPD-negative donors IFN-γ median values were lower than those from PPD-positive donors, significant
differences only being established when MTB was used as antigen.
Conclusions
The specific cellular immune response against MAs in TB patients described here for the first time suggests a potential
immunoprotective role for MAs.
60 ESM 2009