CD4+ CCR5+ and CD4+ CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis.
The potential involvement of apoptosis in the pathogenesis of visceral leishmaniasis (VL) was examined by studying spontaneous and Leishmania antigen (LAg)-induced apoptosis using cryopreserved peripheral blood mononuclear cells (PBMC) of Sicilian patients with VL. Results indicate that monocytes and T lymphocytes from acute VL patients show a significantly higher level of apoptosis compared with that observed in healed subjects. The percentage of apoptotic cells was higher in monocytes than in T lymphocytes. T cells involved in programmed cell death (PCD) were mainly of the CD4(+) phenotype. In particular, the T helper 1-type (Th1) subset, as evaluated by chemokine receptor-5 (CCR5) expression, is involved in this process. Cell death in Th1-type uses a CD95-mediated mechanism. Furthermore, Th1-type CCR5(+) cells are prone to cell suicide in an autocrine or paracrine way, as attested by enhanced expression of CD95L in acute VL patients. The reduction in Th1-type cells by apoptosis was confirmed by the decrease in interferon-gamma secretion. In conclusion, apoptosis of monocytes, CD4(+) and CD4(+) CCR5(+) T cells could be involved in the failure of cell mediated immunity that is responsible for severe immune-depression in VL.
Potestio
Marcella
M
Department of BioPathology and BioMedical Methodologies, University of Palermo, Palermo, Italy.
D'Agostino
Pietro
P
Romano
Giuseppina Colonna
GC
Milano
Salvatore
S
Ferlazzo
Viviana
V
Aquino
Alessandra
A
Di Bella
Gloria
G
Caruso
Rosalba
R
Gambino
Giuseppe
G
Vitale
Giustina
G
Mansueto
Serafino
S
Cillari
Enrico
E
D000208:Acute Disease; D000328:Adult; D000953:Antigens, Protozoan / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D000953:Antigens, Protozoan; C515350:CCR3 protein, human; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D019014:fas Receptor