title: Role of CD8(+) T cells in triggering reversal reaction in HIV/leprosy patients.
abstract: It has been reported that the initiation of highly active anti-retroviral therapy (HAART) is associated with the development of reversal reaction (RR) in co-infected HIV/leprosy patients. Nevertheless, the impact of HIV and HAART on the cellular immune response to Mycobacterium leprae (ML) remains unknown. In the present study, we observed that ex vivo peripheral blood mononuclear cells (PBMCs) of both RR and RR/HIV patients presented increased percentages of activated CD4(+) T cells when compared with the healthy individuals (HC) group. The frequency of CD8(+)  CD38(+) cells increased in the PBMCs of RR/HIV patients but not in RR patients when compared with the HC group. Both RR and RR/HIV skin lesion cells presented similar percentages of activated CD4(+) cells, but the numbers of activated CD8(+) cells were higher in RR/HIV in comparison to the RR group. The frequency of interferon-γ-producing cells was high in response to ML regardless of HIV co-infection. In ML-stimulated cells, there was an increase in central memory CD4(+) T-cell frequencies in the RR and RR/HIV groups, but an increase in central memory CD8(+) T-cell frequency was only observed in the RR/HIV group. ML increased granzyme B(+) effector memory CD8(+) T-cell frequencies in the RR/HIV PBMCs, but not in the HC and RR groups. Our data suggest that the increased expression of effector memory CD8(+) T cells, together with greater perforin/granzyme B production, could be an additional mechanism leading to the advent of RR in co-infected patients. Moreoever, this increased expression may explain the severity of RR occurring in these patients.
authors.affiliation: Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Ariane Leite
authors.initials: AL
authors.lastname: de Oliveira
authors.forename: Thaís Porto
authors.initials: TP
authors.lastname: Amadeu
authors.forename: Andressa Cristina
authors.initials: AC
authors.lastname: de França Gomes
authors.forename: Vinícius Martins
authors.initials: VM
authors.lastname: Menezes
authors.forename: José Augusto
authors.initials: JA
authors.lastname: da Costa Nery
authors.forename: Roberta Olmo
authors.initials: RO
authors.lastname: Pinheiro
authors.forename: Euzenir Nunes
authors.initials: EN
authors.lastname: Sarno
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D053804:Granzymes / Q000096:biosynthesis; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D056005:Leprosy, Paucibacillary / Q000150:complications* / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology; D015213:Neuroimmunomodulation; D054353:Perforin / Q000096:biosynthesis; D012867:Skin / Q000276:immunology; D055815:Young Adult
chemical_list: D008562:Membrane Glycoproteins; D054353:Perforin; D007371:Interferon-gamma; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; C509213:GZMB protein, human; D053804:Granzymes
keywords: CD8+ T cells; HIV; leprosy; reversal reaction