Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue.

Abstract

It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever (DHF) is much more commonly observed during secondary dengue virus infections than primary infections. In order to elucidate the role of T lymphocytes in the pathogenesis of DHF, we attempted to determine whether T lymphocytes are activated in vivo during dengue virus infections, by examining the levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon-'y (IFN'y) in the sera of 59 patients with DHF and 41 patients with dengue fever (DF).The levels of sIL-2R, sCD4, sCD8, IL-2, and IFNy were significantly higher in the acute sera of patients with DHF than in the sera of healthy children (P < 0.001 for all markers). The acute sera of patients with DF contained higher levels of sIL-2R, sCD4, IL-2, and IFN-y than the sera of healthy children (P < 0.001 for sIL-2R, IL-2, and IFN-y; P < 0.05 for sCD4), but did not have elevated levels of sCD8. The levels of sIL-2R (P < 0.05), sCD4 (P < 0.001), and sCD8 (P < 0.001) were higher in DHF than in DF on days 3-4 after the onset of fever. The levels of IL-2 and IFN'y in patients with DHF were highest 1 d before defervescence. There were no significant differences in the levels of sIL-2R, sCD4, sCD8, IL-2, and IFNy among grades 1, 2, and 3 of DHF. These results indicate (a) T lympho-

Uveitis following dengue fever

“…6,7 In addition, these inflammatory mediators cause capillary leakage and breakdown of the blood aqueous barrier, resulting in anterior uveitis. 15,16 All of the patients in this case series presented with an acute infection between October, 2006 and January, 2007. All of them had DF and not DHF/DSS.…”

Timing of CD8+ T Cell Responses in Relation to Commencement of Capillary Leakage in Children with Dengue

“…Relatively higher levels of various proinflammatory cytokines and their receptors and soluble CD4/8 are found in acute sera of children with DHF compared with children with DF (18,30,31). DHF patients also have a greater percentage of CD8 + T cells bearing the early activation marker CD69 + than DF patients during the febrile phase (19).…”

Variation in Inflammatory/Regulatory Cytokines in Secondary, Tertiary, and Quaternary Challenges with Dengue Virus

“…Because over-expression of pro-inflammatory cytokines and over-activation of the immune system during heterologous secondary infection has been associated with severe dengue, [63][64][65][66] the secondary homologous protective response could be associated with a balanced inflammatory/regulatory response. [67][68][69] Regulatory activities of the cytokines are probably crucial in controlling the inflammatory response during dengue disease, which is necessary for control of viral infection, and the balance among inflammatory/regulatory mediators could be related to recovery of most patients with a dengue secondary infection.…”