Role of CD8⁺ T cells in triggering reversal reaction in HIV/leprosy patients

Abstract

Summary 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.

Role of TEFFECTOR/MEMORY Cells, TBX21 Gene Expression and T-Cell Homing Receptor on Type 1 Reaction in Borderline Lepromatous Leprosy Patients

“…Similar findings were disclosed by Oliveira et al ., who also demonstrated an increase in both CD4+ and CD8+ TEMRA cells in peripheral blood leucocytes in co-infected HIV/leprosy patients showing T1R. Authors also suggested that CD8+ T EM cells triggered T1R in HIV/leprosy patients [ 23 ].…”

Leprosy As a Complex Infection: Breakdown of the Th1 and Th2 Immune Paradigm in the Immunopathogenesis of the Disease

“…T CD8+ lymphocytes are primarily involved in the development of cytotoxicity ( 50 , 51 ). Studies have shown that T CD8+ cells participate in mechanisms that lead to the destruction of the bacillus in coinfection with HIV in a reverse reaction ( 52 , 53 ). In this context, by recognizing virus-infected cells, T CD8+ cells would promote the release of granzymes and perforins that destroy the coinfected cells in patients with a type-1 reverse reaction ( 52 , 53 ).…”

“…Studies have shown that T CD8+ cells participate in mechanisms that lead to the destruction of the bacillus in coinfection with HIV in a reverse reaction ( 52 , 53 ). In this context, by recognizing virus-infected cells, T CD8+ cells would promote the release of granzymes and perforins that destroy the coinfected cells in patients with a type-1 reverse reaction ( 52 , 53 ). The response of B lymphocytes is primarily associated with the humoral response, and some studies on leprosy have demonstrated increased expression of CD20 in the tuberculoid form and borderline tuberculoid form in a reverse reaction ( 40 , 54 ).…”

Correlation between Central Memory T Cell Expression and Proinflammatory Cytokine Production with Clinical Presentation of Multibacillary Leprosy Relapse

“…Similar to our findings, Oliveira et al also demonstrated an increase in CD8+ T CM cells in co-infected HIV/leprosy patients showing an acute inflammatory manifestation referred to as reversal reaction. The authors also suggested that CD8+ T CM cells may contribute to these episodes [ 27 ]. Interestingly, the negative CD86 expression on both APC did not prevent the significant increase in both CD4+ and CD8+ T CM cells in our patients in response to the ML antigen.…”