Immunophenotype of skin lymphocytic infiltrate in patients co-infected with Mycobacterium leprae and human immunodeficiency virus: a scenario dependent on CD8+ and/or CD20+ cells

Massone, Cesare; Talhari, Carolina; Talhari, Sinésio; Brunasso, Alexandra Maria Giovanna; Campbell, Tom; Curcic, P.; Cerroni, Lorenzo; Ribeiro‐Rodrigues, Rodrigo

doi:10.1111/j.1365-2133.2011.10412.x

Cited by 13 publications

(14 citation statements)

References 28 publications

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“…Furthermore, the increased frequency in T‐cell activation markers in RR and RR/HIV might also be explained by the fact that immune activation could be determined by ML. As in recent studies showing a higher frequency of CD8 + T cells in the borderline tuberculoid/HIV granuloma of HIV patients, our data demonstrated a higher frequency of CD8 + T cells in RR/HIV granulomas.…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2013

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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.

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Section: Discussionsupporting

confidence: 90%

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

et al. 2013

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“…Unlike HIV-negative patients with leprosy, patients co-infected with HIV and leprosy present an almost exclusive CD8+ cytotoxic infiltrate at both tuberculoid and lepromatous poles of the disease. 22 …”

Section: Discussionmentioning

confidence: 99%

T regulatory cells (TREG)(TCD4+CD25+FOXP3+) distribution in the different clinical forms of leprosy and reactional states

Parente

Talhari

Schettini

et al. 2015

An. Bras. Dermatol.

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BACKGROUNDLeprosy is characterized histologically by a spectrum of different granulomatous skin lesions, reflecting patients' immune responses to Mycobacterium leprae. Although CD4+CD25+ FoxP3+ T regulatory cells are pivotal in the immuneregulation, presence, frequency, and distribution of Tregs in leprosy, its reactional states have been investigated in few studies.OBJECTIVESThis study aimed to verify the frequency and distribution of regulatory T cells in different clinical forms and reactional states of leprosy.METHODSWe performed an immunohistochemical study on 96 leprosy cases [Indeterminate (I): 9 patients; tuberculoid tuberculoid: 13 patients; borderline tuberculoid: 26 patients; borderline borderline: 3 patients; borderline lepromatous: 8 patients; lepromatous lepromatous: 27 patients; reversal reaction: 8 patients; and erythema nodosum leprosum: 2 patients].RESULTSFoxP3-positive cells were present in 100% of the cases with an average density of 2.82% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was a statistically significant increment of FoxP3 expression in patients with leprosy reversal reactions when compared with patients presenting with type I leprosy (P= 0.0228); borderline tuberculoid leprosy (P = 0.0351) and lepromatous leprosy (P = 0.0344).CONCLUSIONSThese findings suggest that Tregs play a relevant role in the etiopathogenesis of leprosy, mainly in type I leprosy reaction.

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“…In a study by AS Pereira et al [15] the clinical, immunologic, histopathologic, and virologic features among 22 HIV-1-leprosy-coinfected Brazilian patients indicate that each disease progressed as in single infection [15]. Despite overall HIV-associated immunosuppression, cell-mediated immune responses to M. leprae are well preserved at the site of the disease [16]. In our patient, the disease progressed slowly, and the lesions did not alter morphologically over a period of 4 years of followup.…”

Section: Discussion: Leprosy In Hiv-1 Diseasementioning

confidence: 99%

Human Immunodeficiency Virus and Leprosy Coinfection: Challenges in Resource-Limited Setups

Kwobah

Wools‐Kaloustian

Gitau

et al. 2012

Case Reports in Medicine

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Mycobacteria leprae(leprosy) and HIV coinfection are rare in Kenya. This is likely related to the low prevalence (1 per 10,000 of population) of leprosy. Because leprosy is no longer a public health challenge there is generally a low index of suspicion amongst clinicians for its diagnosis. Management of a HIV-1-leprosy-coinfected individual in a resource-constrained setting is challenging. Some of these challenges include difficulties in establishing a diagnosis of leprosy; the high pill burden of cotreatment with both antileprosy and antiretroviral drugs (ARVs); medications' side effects; drug interactions; scarcity of drug choices for both diseases. This challenge is more profound when managing a patient who requires second-line antiretroviral therapy (ART). We present an adult male patient coinfected with HIV and leprosy, who failed first-line antiretroviral therapy (ART) and required second-line treatment. Due to limited choices in antileprosy drugs available, the patient received monthly rifampicin and daily lopinavir-/ritonavir-based antileprosy and ART regimens, respectively. Six months into his cotreatment, he seemed to have adequate virological control. This case report highlights the challenges of managing such a patient.

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Immunophenotype of skin lymphocytic infiltrate in patients co-infected with Mycobacterium leprae and human immunodeficiency virus: a scenario dependent on CD8+ and/or CD20+ cells

Abstract: Data presented here suggest that cell-mediated immune responses to M. leprae are preserved at the site of disease and that in the absence of CD4+ cells, CD8+FOXP3+ and CD20+ cells may be involved in granuloma formation.

Cited by 13 publications

References 28 publications

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

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

T regulatory cells (TREG)(TCD4+CD25+FOXP3+) distribution in the different clinical forms of leprosy and reactional states

Human Immunodeficiency Virus and Leprosy Coinfection: Challenges in Resource-Limited Setups

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Immunophenotype of skin lymphocytic infiltrate in patients co-infected with Mycobacterium leprae and human immunodeficiency virus: a scenario dependent on CD8+ and/or CD20+ cells

Abstract: Data presented here suggest that cell-mediated immune responses to M. leprae are preserved at the site of disease and that in the absence of CD4+ cells, CD8+FOXP3+ and CD20+ cells may be involved in granuloma formation.

Cited by 13 publications

References 28 publications

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

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

T regulatory cells (TREG)(TCD4+CD25+FOXP3+) distribution in the different clinical forms of leprosy and reactional states

Human Immunodeficiency Virus and Leprosy Coinfection: Challenges in Resource-Limited Setups

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

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