CD4+CD25+ T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells.
Endogenous regulatory T (Treg) cells are involved in the control of infections, including Leishmania infection in mice. Leishmania viannia braziliensis is the main etiologic agent of cutaneous leishmaniasis (CL) in Brazil, and it is also responsible for the more severe mucocutaneous form. Here, we investigated the possible involvement of Treg cells in the control of the immune response in human skin lesions caused by L. viannia braziliensis infection. We show that functional Treg cells can be found in skin lesions of patients with CL. These cells express phenotypic markers of Treg cells--such as CD25, cytotoxic T lymphocyte-associated antigen 4, Foxp3, and glucocorticoid-induced tumor necrosis factor receptor--and are able to produce large amounts of interleukin-10 and transforming growth factor- beta . Furthermore, CD4+CD25+ T cells derived from the skin lesions of 4 of 6 patients with CL significantly suppressed in vitro the phytohemagglutinin-induced proliferative T cell responses of allogeneic peripheral-blood mononuclear cells (PBMCs) from healthy control subjects at a ratio of 1 Treg cell to 10 allogeneic PBMCs. These findings suggest that functional Treg cells accumulate at sites of Leishmania infection in humans and possibly contribute to the local control of effector T cell functions.
Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.
Ana P
AP
Campanelli
Ana M
AM
Roselino
Karen A
KA
Cavassani
Marcelo S F
MS
Pereira
Renato A
RA
Mortara
Claudia I
CI
Brodskyn
Heitor S
HS
Goncalves
Yasmine
Y
Belkaid
Manoel
M
Barral-Netto
Aldina
A
Barral
Joao S
JS
Silva
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis*; D019742:Chemokines, CC / Q000378:metabolism; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000378:metabolism; D007892:Leishmania braziliensis; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D012867:Skin / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
C515354:CCR4 protein, human; D015704:CD4 Antigens; D019742:Chemokines, CC; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10