title: Differential expression of the costimulatory molecules CD86, CD28, CD152 and PD-1 correlates with the host-parasite outcome in leprosy.
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.
authors.affiliation: Laboratório de Investigação Médica, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Maria de Lourdes
authors.initials: Mde L
authors.lastname: Palermo
authors.forename: Maria Ângela Bianconcini
authors.initials: MÂ
authors.lastname: Trindade
authors.forename: Alberto José da Silva
authors.initials: AJ
authors.lastname: Duarte
authors.forename: Camila Rodrigues
authors.initials: CR
authors.lastname: Cacere
authors.forename: Gil
authors.initials: G
authors.lastname: Benard
mesh_terms: D000328:Adult; D051940:B7-2 Antigen / Q000276:immunology* / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006790:Host-Parasite Interactions; D006801:Humans; D007918:Leprosy / Q000276:immunology / Q000382:microbiology*; D008297:Male; D009166:Mycobacterium leprae / Q000276:immunology* / Q000502:physiology; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor