Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis.
Cutaneous (CL) and mucosal leishmaniasis (ML) are characterized by a predominant type 1 immune response (IFN-gamma and TNF-alpha production) and strong inflammatory response in the lesions with few parasites. This exacerbated type 1 response is more evident in ML as compared to CL. Our main hypothesis is that a differential immune regulation of T cell activation leads to over reactive T cells in ML. In the present study, we investigated immunological factors that could explain the mechanisms behind it by comparing some immune regulatory mechanisms between ML and CL patients: frequency of cells expressing co-stimulatory molecules, apoptotic markers, T cell activation markers; and ability of neutralizing antibodies to IL-2, IL-12 and IL-15 do down-regulate IFN-gamma production in leishmania antigen-stimulated peripheral blood mononuclear cells (PBMC). Interestingly, in CL anti-IL-2 and anti-IL-15 significantly suppressed antigen-specific IFN-gamma production, while in ML only anti-IL-2 suppressed IFN-gamma production. Finally, higher frequency of CD4+ T cells expressing CD28-, CD69+ and CD62L(low) were observed in ML as compared to CL. These data indicate that an exacerbated type 1 response in ML is differentially regulated and not appropriately down modulated, with increased frequencies of activated effectors T cells, maintaining the persistent inflammatory response and tissue damage observed in ML.
Carvalho
L P
LP
Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Passos
S
S
Bacellar
O
O
Lessa
M
M
Almeida
R P
RP
Magalhães
A
A
Dutra
W O
WO
Gollob
K J
KJ
Machado
P
P
de Jesus
A Ribeiro
AR
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000494:pharmacology; D060908:CTLA-4 Antigen; D002648:Child; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D019409:Interleukin-15 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D016773:Leishmaniasis, Cutaneous / Q000209:etiology / Q000276:immunology*; D007897:Leishmaniasis, Mucocutaneous / Q000209:etiology / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma