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

Luciana Nahar Dos Santos,Iris Maria Peixoto Alvim,José Augusto Da Costa Nery,Pedro Henrique Lopes Da Silva,Euzenir Nunes Sarno,Danuza Esquenazi,Flávio Alves Lara

doi:10.1371/journal.pone.0164543

Luciana Nahar Dos Santos, Iris Maria Peixoto Alvim + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0164543

Copy DOI

Abstract

In spite of hyporesponsivity to Mycobacterium leprae, borderline lepromatous (BL) patients show clinical and immunological instability, and undergo frequent acute inflammatory episodes such as type 1 reaction (T1R), which may cause nerve damages. This work focused on the participation of T cell subsets from blood and skin at T1R onset. We observed a significantly increased ex vivo frequency of both effector and memory CD4+ and CD8+ T cells in T1R group. Besides, ex vivo frequency of T cell homing receptor, the Cutaneous Leukocyte-associated Antigen (CLA) was significantly increased in T cells from T1R patients. M. leprae induced a higher frequency of CD4+ TEM and CD8+ TEF cells, as well as of CD8+/TEMRA (terminally differentiated effector T cells) subset, which expressed high CD69+. The presence of IFN-γ‒producing-CD4+ TEF and naïve and effector CD8+ T lymphocytes was significant in T1R. TBX21 expression was significantly higher in T1R, while BL showed increased GATA3 and FOXP3 expression. In T1R, TBX21 expression was strongly correlated with CD8+/IFN-γ‒ T cells frequency. The number of double positive CD8+/CLA+ and CD45RA+/CLA+ cells was significantly higher in skin lesions from T1R, in comparison with non-reactional BL group. The observed increase of ex vivo T cells at T1R onset suggests intravascular activation at the beginning of reactional episodes. The antigen-specific response in T1R group confirmed the higher number of CD8+/CLA+ and CD45RA+/CLA+ cells in T1R lesions suggests possible migration of these cells activated by M. leprae components inside the vascular compartment to skin and participation in T1R physiopathology.

Highlights

Leprosy is a chronic infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae, which affects about 200,000 new individuals worldwide [1]
According to Ridley and Jopling criteria [18], all leprosy patients examined in this study were classified by two experienced pathologists as borderline lepromatous (BL) or type 1 reaction (T1R)
T1R group showed a mean age of 41.25 years-old, while BL group presented a mean age of 44.3 years-old

Summary

Introduction

Leprosy is a chronic infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae, which affects about 200,000 new individuals worldwide [1]. M. leprae preferably infects skin macrophages and Schwann cells from peripheral nerves, and the variety of clinical and pathological features of the disease according to the host immune response gives rise to a spectrum of polar forms. Patients showing anergy or hyporesponsivity to M. leprae antigens and present disseminated lesions with high bacillary load, as opposed to tuberculoid ones, who exhibit a preserved specific cellular immune response, with limited lesions and a restricted growth of the pathogen. The major cause of deformities and neural disabilities in leprosy relates to immune reactions that affect 30–50% of patients during the clinical course of the disease. Reactional episodes are characterized by a sudden, intense and unregulated inflammatory response, being subdivided into Reversal Reaction (T1R or RR) and Erythema Nodosum Leprosum (T2R or ENL) [3, 4]

Objectives

Methods

Results

Discussion

Conclusion