Lymphocyte activation and subset redistribution in the peripheral blood in acute malaria illness: distinct γδ+ T cell patterns in Plasmodium falciparum and P. vivax infections

Abstract

SUMMARYLymphocyte subset distributions and activation in the peripheral blood were studied in 39 patients with acute malaria and 16 healthy controls from Addis Ababa and Nazareth, Ethiopia. As confirmed by polymerase chain reaction (PCR), 15 patients were infected with Plasmodium falciparum (Pf ), 17 with P. vivax (Pv) and seven were double-infected (Di) with both Pf and Pv. Three-colour flow cytometry was used for phenotyping. Total leucocyte and lymphocyte counts were lower in malaria patients than in controls. The T cell count was reduced in Pf patients, while in the Pv and Di patients there was a reduction in the natural killer (NK) cell count. The CD4/CD8 ratio remained unchanged. gd + T cells were significantly elevated in Pf and Di patients, but not in Pv patients. The increase in gd + T cells was mostly due to an increase in Vd1 + cells. Analyses of cellular activation indicated by the expressions of CD25 and HLA-DR revealed significantly higher numbers of activated CD3 + cells, including gd + T cells, in all patient groups compared with controls. Our results thus indicate that in acute malaria illness there is a complex pattern of change in lymphocyte subset distribution and activation, including gd + T cells. These patterns in Pf infection seem to be distinct from those in Pv infection.

Enhanced T cell activation in Plasmodium falciparum malaria-infected human immunodeficiency virus-1 patients from Mozambique

“…In this study, Pf/HIV co-infected patients exhibited the highest percentages of HLA-DR and CD38 on the CD3 + and CD8 + T lymphocytes, respectively. Indeed, malaria patients had higher percentages of CD38 on CD8 + and HLA-DR on CD3 + T cells than did the healthy subjects, confirming previous data that malaria itself contributes to activation (Worku et al 1997). Although dual-positive CD38/HLA-DR on CD8 + T cells is a more accurate measure of the activation state, when both molecules were analysed separately, they displayed the same profile.…”

“…Acute malaria elevates the HIV viral load (VL), which in turn can enhance the risk for HIV transmission ). In addition, Plasmodium antigens lead to strong cellular activation (Worku et al 1997) which may facilitate de novo HIV-1 infection and replication (Froebel et al 2004). The preference of HIV-1 for infecting activated memory CD4 + T lymphocytes can increase cell death (Grossman et al 2002).…”

“…Cell activation is one of the crucial mechanisms in the pathogenesis of both malaria (Worku et al 1997) and HIV-1/AIDS (Douek et al 2009). The release of pro-inflammatory cytokines due to increased T cell activation during acute malaria has been implicated in the clinical complications and contributes to a disruption in the balance of effector/regulatory immune state (Ayimba et al 2011, Davenport et al 2012).…”

Altered cord blood γδ T cell repertoire in Nigeria: Possible impacts of environmental factors on neonatal immunity

“…First, malaria prevalence is high in Jos (Egwunyenga et al, 2001;Egwunyenga et al, 1997). Second, malaria has documented effects on adult γδ T cells, including expansion of peripheral blood subsets for endemic infections (Hviid et al, 2001;Worku et al, 1997) and specific depletion of Vγ2Jγ1.2 cells in naïve individuals (traveler's malaria) (Martini et al, 2003); fetuses are immunologically naïve and plasmodia exposure might have an impact similar to infection of naïve adults. Third, P. falciparum produces small stimulatory phosphoantigens (Behr et al, 1996) (approximately 200 dalton) that might easily cross the placental barrier and trigger fetal responses.…”

Plasmodium vivax Blood-Stage Dynamics

“…Recent studies indicate that Duffy-antigen expression is higher on reticulocytes (Woolley et al, 2000), that gametocyte production and infectivity in P. falciparum are higher in reticulocytotic blood, e.g., from sickle-cell anemics (Trager and Gill, 1992;Drakeley et al, 1999;Trager et al, 1999), that P. falciparum infectivity increases with the proportion of male gametocytes (Robert, Read et al, 1996), and that stimulation of erythropoesis, but not reticulocytosis per se, shifts gametocyte sex ratios in P. gallinaceum and P. vinckei toward males (Paul et al, 2000). This new conjunction suggests possible links to the homeostatic mechanisms that boost reticulocyte production in response to red blood cell depletion and potential insights into the within-and between-host dynamics of mixed-species Plasmodium infections (Snewin et al, 1991;Bossert, 1997, 1999;Worku et al, 1997;Mason and McKenzie, 1999). In Aotus monkeys, for instance, prior infection with either P. falciparum or P. vivax increases the infectivity of a subsequent infection with the other species (Collins et al, 1979).…”