02975nas a2200493 4500000000100000008004100001260001300042653002600055653001000081653004200091653003100133653003100164653001100195653001400206653001900220653001100239653002300250653002300273653002100296653002800317653002600345653000900371653002700380653001600407653002500423653002600448653001300474653000900487653001600496100001600512700001400528700002100542700001500563700001800578700001500596700001200611245008400623856007700707300001000784490000800794050001800802520164700820022001402467 2013 d c2013 Sep10aADP-ribosyl Cyclase 110aAdult10aAntiretroviral Therapy, Highly Active10aCD4-Positive T-Lymphocytes10aCD8-Positive T-Lymphocytes10aFemale10aGranzymes10aHIV Infections10aHumans10aImmunity, Cellular10aImmunologic Memory10aInterferon-gamma10aLeprosy, Paucibacillary10aLymphocyte Activation10aMale10aMembrane Glycoproteins10aMiddle Aged10aMycobacterium leprae10aNeuroimmunomodulation10aPerforin10aSkin10aYoung Adult1 aOliveira AL1 aAmadeu TP1 aFrança Gomes AC1 aMenezes VM1 aCosta Nery JA1 aPinheiro R1 aSarno E00aRole of CD8(+) T cells in triggering reversal reaction in HIV/leprosy patients. uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809705/pdf/imm0140-0047.pdf a47-600 v140 aOLIVEIRA 20133 a

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.

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