Differential expression of the costimulatory molecules CD86, CD28, CD152 and PD-1 correlates with the host-parasite outcome in leprosy

Maria de Lourdes Palermo,Camila Rodrigues Cacere,Maria Ângela Bianconcini Trindade,Gil Benard,Alberto José da Silva Duarte

doi:10.1590/s0074-02762012000900024

Abstract

Leprosy is a spectral disease exhibiting two polar sides, namely, lepromatous leprosy (LL) characterised by impaired T-cell responses and tuberculoid leprosy in which T-cell responses are strong. Proper T-cell activation requires signalling through costimulatory molecules expressed by antigen presenting cells and their ligands on T-cells. We studied the influence of costimulatory molecules on the immune responses of subjects along the leprosy spectrum. The expression of the costimulatory molecules was evaluated in in vitro-stimulated peripheral blood mononuclear cells of lepromatous and tuberculoid patients and healthy exposed individuals (contacts). We show that LL patients have defective monocyte CD86 expression, which likely contributes to the impairment of the antigen presentation process and to patients anergy. Accordingly, CD86 but not CD80 blockade inhibited the lymphoproliferative response to Mycobacterium leprae. Consistent with the LL anergy, there was reduced expression of the positive signalling costimulatory molecules CD28 and CD86 on the T-cells in these patients. In contrast, tuberculoid leprosy patients displayed increased expression of the negative signalling molecules CD152 and programmed death-1 (PD-1), which represents a probable means of modulating an exacerbated immune response and avoiding immunopathology. Notably, the contacts exhibited proper CD86 and CD28 expression but not exacerbated CD152 or PD-1 expression, suggesting that they tend to develop a balanced immunity without requiring immunosuppressive costimulatory signalling.

Highlights

The prevalence of leprosy has been decreasing all over the world, hyper-endemic areas persist where the transmission of leprosy is still out of control (WHO 2010)
Proliferative responses - The Table shows that the peripheral blood mononuclear cells (PBMCs) of patients with the lepromatous form of leprosy were anergic to MLCwA, while positive responses were observed for the tuberculoid patients and contacts
The blockade of CD86 signalling, but not the blockade of CD80 signalling, with a neutralising monoclonal antibody resulted in significant inhibition of the proliferative response to M. leprae antigens

Summary

Introduction

The prevalence of leprosy has been decreasing all over the world, hyper-endemic areas persist where the transmission of leprosy is still out of control (WHO 2010). A model of T-cell costimulation has been proposed in which the distinct structures and binding properties of CD86 and CD80 significantly enhance the activating and inhibitory functions of CD28 and CD152, respectively (Collins et al 2002) This seems to be relevant to the regulation of the immune responses in several clinical conditions. Other costimulatory molecules have been described that influence the subsequent adaptive immune responses, such as programmed death-1 (PD-1) and inducible costimulatory protein (ICOS) (Greenwald et al 2005) These molecules have been shown to play major roles in triggering autoimmunity or peripheral tolerance and directing the protective immune response to pathogens or facilitating the persistence of the parasite leading to chronic immune activation (Zhu et al 2011, Bour-Jordan et al 2011). The expression levels of the costimulatory molecules CD80, CD86, CD28, CD152, PD-1 and ICOS were evaluated in in vitro-stimulated peripheral blood mononuclear cells (PBMCs) from both lepromatous and tuberculoid patients and healthy exposed individuals

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Conclusion