Estudo in situ da heterogeneidade de mastócitos e células T reguladoras em pacientes com hanseníase, com e sem episódios reacionais
Nenhuma Miniatura disponível
Data
2014-02-26
Autores
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal de Goiás
Resumo
Leprosy is a complex, chronic, infectious dermato-neurological disease that affects the
skin and peripheral nerves especially during acute immune-inflammatory episodes
known as type 1/T1R and type 2/T2R reactions. There is no experimental model for
leprosy and leprosy skin lesions have been extensively used to unravel its multifaceted
immunopathological mechanisms.This study investigated in situ expression of two
distinct cell populations with important immunoregulatory roles: T regulatory (Treg)
cells and mast cells (MC) in diverse skin diseases with emphasis on leprosy T1R and
T2R. For the Treg cell study, 154 skin biopsies from 114 participants belonging to 3
groups were investigated: 1. Leprosy (n=74), 56 T1R (28-paired biopsies reactionfree/reactional
from the same patient, 28 single reactional biopsy), 18 T2R (12 pairedreaction-free/reactional
lesions, 6 single reactional biopsy); 2. Dermatoses: (n=29) noninfectious
and cutaneous infectious diseases; 3. Normal controls: skin fragment of
mammoplasty from healthy females that had cosmetic surgery. Double
immunohistochemical detection of Treg cells was performed with automated platform
for CD25 and Foxp3 staining. Quantifications of double immunostained Treg cells was
performed (values expressed by mm2
) blinded to the participants’ clinical status. For
the mast cell study 80 skin biopsies from 3 groups were investigated: 40 newly
diagnosed untreated leprosy patients (18 reaction-free, 11 T1R, 11 T2R), 29 patients
with other dermatoses (the same as for Treg study) and 11 normal skins. Toluidine blue
stained intact and degranulated MC counts/mm2
; streptavidin-biotin-peroxidase
immunostaining was used to detect tryptase/try+
and chymase/chy+ MCs and their
density (median optical density) was evaluated. Results: Treg study: Not one
CD25+
Foxp3+
Treg cell was seen in any of the 11 normal skin sections while variable
numbers were detected in skin diseases (p<0.0001); the number of double stained cells
was higher in infectious compared to non-infectious diseases (p=0.008). Treg cell
numbers were comparable between leprosy and other infectious dermatoses (p=0.157)
Treg cell counts in reactional lesions were higher than in reaction-free leprosy lesions
(p<0.002). Paired biopsies of T1R or T2R reactional/reaction-free lesions showed
xxvii
increased numbers of Treg during T1R compared to reaction-free lesions from the same
patient (p< 0.001). Treg cell median in T1R developed during MDT was slightly higher
compared to T1R developed at diagnosis in naïve patients (p=0.047). There was a trend
in increasing Treg cell numbers from the tuberculoid to borderline-lepromatous form,
which showed the highest median value of Tregs, however this difference was not
significant (p>0.8). Mast cell study: Infectious and non-infectious skin lesions showed
higher numbers of degranulated than intact MC both for leprosy and other dermatoses,
compared to normal skin. The numbers of degranulated MC were higher than intact MC
regardless of the leprosy form (from tuberculoid/TT to lepromatous/LL), regardless of
the occurrence of leprosy reactions (reactional and reaction-free) and regardless of the
type of reaction (T1R/T2R). Try+ MC numbers and density were higher than chy+ MC
in leprosy, in reaction-free and reactional lesions, particularly in T2R, but not in other
dermatoses. Conclusions: Higher Treg numbers seen in T1R suggest Treg role in
suppressing the exacerbated cell-mediated phenomenon that causes T1R. Differential
expression/ of try+
and chy+ MC subsets was seen in leprosy compared to other skin
diseases and to normal skin. However, neither leprosy form nor leprosy reaction was
associated with MC changes in lesions suggesting that the Mycobacterium leprae
infectious process per se dictates MC expression in leprosy skin lesions.
Descrição
Palavras-chave
Células Treg , Mastócitos , Triptase , Quimase , Hanseníase , Dermatose , Treg , Mast cell , Tryptase , Chymase , Leprosy , Skin diseases
Citação
COSTA, M. B. Estudo in situ da heterogeneidade de mastócitos e células T reguladoras em pacientes com hanseníase, com e sem episódios reacionais. 2014. 156 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2014.