Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease.
The immune mechanisms involved in dengue fever and dengue hemorrhagic/dengue shock syndrome are not well understood. The ex vivo activation status of immune cells during the dengue disease in patients was examined. CD4 and CD8 T cells were reduced during the acute phase. Interestingly, CD8 T cells co-expressing activation marker HLA-DR, Q, P, and cytolytic granule protein-Tia-1 were significantly higher in dengue patients than in controls. Detection of adhesion molecules indicated that in dengue patients the majority of T cells (CD4 and CD8) express the activation/memory phenotype, characterized as CD44HIGH and lack the expression of the naïve cell marker, CD62L LOW. Also, the levels of T cells co-expressing ICAM-1 (CD54), VLA-4, and LFA-1 (CD11a) were significantly increased. CD8 T lymphocytes expressed predominantly low levels of anti-apoptotic molecule Bcl-2 in the acute phase, possibly leading to the exhibition of a phenotype of activated/effector cells. Circulating levels of IL-18, TGF-b1 and sICAM-1 were significantly elevated in dengue patients. Early activation events occur during acute dengue infection which might contribute to viral clearance. Differences in expression of adhesion molecules among CD4 and CD8 T cells might underlie the selective extravasation of these subsets from blood circulation into lymphoid organs and/or tissues. In addition, activated CD8 T cells would be more susceptible to apoptosis as shown by the alteration in Bcl-2 expression. Cytokines such as IL-18, TGF-b1, and sICAM-1 may be contributing by either stimulating or suppressing the adaptative immune response, during dengue infection, thereby perhaps establishing a relationship with disease severity.
Azeredo
Elzinandes L
EL
Laboratório de Imunologia Viral, Departamento de Virologia, Instituto Oswaldo Cruz, Fiocruz.
Zagne
Sonia M O
SM
Alvarenga
Allan R
AR
Nogueira
Rita M R
RM
Kubelka
Claire F
CF
de Oliveira-Pinto
Luzia M
LM
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D015415:Biomarkers; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines