Modulation of T-cell responses by dendritic cells in tuberculosis patients

PASQUINELLI VIRGINIA; QUIROGA FLORENCIA; MARTÍNEZ GUSTAVO; JURADO JAVIER; ROLDÁN N; MUSELLA ROSA; CASTRO ZORRILLA LILIANA; ABBATE EDUARDO; GARCIA VERÓNICA

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología; 2005

SAI

Antigen presenting cell-interaction with Mycobacterium tuberculosis (Mtb) is a key feature in tuberculosis (TB). Upon activation, dendritic cells (DCs) strikingly up-regulate SLAM (signaling lymphocytic activation molecule), a costimulatory protein first identified on activated lymphocytes. We previously showed correlation between SLAM expression and T-cell responsiveness to Mtb. Moreover, according to T-cell proliferation, IFN-g and SLAM expression we identified high responder (HR) and low responder (LR) TB patients. Here, we investigated the effect of mycobacterial constituents on SLAM expression and function of DCs from TB patients. Although 19kDa lipoprotein inhibited SLAM expression on DCs from healthy donors (HD), a significant increase in SLAM was detected both in TB patients and HD (p<0.05) after Mtb-DCs maturation. This Mtb-up-regulation of SLAM both on T-cells and DCs might provide a bi-directional signal, increasing pro-inflammatory Th1 responses. Next we investigated the capacity of mature DCs to stimulate T-cells in a Mixed Leukocyte Reaction. Mtb-stimulated DCs from LR patients were able to activate T-cells from responder individuals (IFN-g:985±154 pg/ml), whereas T-cells from LR individuals didn’t respond to HD’s DCs (IFN-g:107±74 pg/ml). Furthermore, 19kDa-DCs maturation didn’t induce T-cell responses, confirming the inhibitory role of 19kDa in the host immune response. Our results suggest that T-cells (but not DCs) are responsible for Mtb-unresponsiveness in LR patients.