T lymphocyte interferon-gamma production induced by Plasmodium falciparum antigen is high in recently infected non-immune and low in immune subjects

Abstract

SUMMARY lnterfcron (IFN) alpha :ind gamma were measured by radio-immunoassays in supernatants from cultures of peripheral blood mononuclear cells (PBMC) or purified T cell subsets incubated wilh either Plasmodium faUiparum schizont-enriched malaria antigen (mAg), uninfected red blood ceils (RBC) or pokewced mitogen (PWM). Cell donors were 24 clinically immune, healthy AfHean adult native residents of a P. falciparum-endemlc region. Haut-Ogoouc. Gabon, and seven non-immune. European temporary residents with a history of a single to a few malaria inleclions during the previous I to 9 months. When PBMC were cultured in medium alone or with RBC antigen no or low titres oriFN-y were detected. PBMC proliferation and IFN-y produetion observed in the presenee of mAg were dose dependent and significantly correlated. When cultured with niAg, PBMC from nonimmune Europeans produced significantly higher levels of IFN-y than did PBMC from clinically immune Africans. No such difference was found when PBMC were cultured with PWM. The mAginduced IFN-'/ production was due mainly to CD4' T eells and was not enhanced by CDS' T cell depletion. No IFTJ-a was deteeted in culture supernatants. Thus, P. falciparum antigens are able to induce in vitro produetion of IFT^I-v by CD4'^ Tcells; however, in this sample, individuals considered to be clinically resi.stant to malaria were low producers of IFN-"/.

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

“…[191]). In contrast, recall responses are markedly increased in malaria patients following a first clinical episode [192][193][194][195]. Indeed, even subclinical infections are sufficient to induce robust IFN-␥ responses to pRBC in previously naïve donors [19,20,42].…”

Regulatory T cells in malaria – friend or foe?

“…In support of this notion, parasite-induced interferon-g (IFN-g) production from peripheral blood mononuclear cells (PBMCs) of clinically immune individuals is considerably less than that from cells derived from semi-immune subjects [6,7]. Whilst the anti-inflammatory cytokine IL-10 and transforming growth factor-b (TGF-b) are clearly important in down-regulating inflammation [8], their cellular origin and the means by which they are induced remain ill defined.…”

Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmission

“…Indeed, ratios of inflammatory to regulatory cytokines seem to determine the severity of disease: low levels of TGF-b [4][5][6] and IL-10 [7,8] have been associated with acute or severe malaria, and high ratios of IFN-g, TNF-a and IL-12 to TGF-b or IL-10 are associated with decreased risk of malaria infection but increased risk of clinical disease in those who do become infected [9,10]. Moreover, in vitro parasite-induced IFN-g production by PBMC is considerably lower among clinically immune individuals than among semi-immune subjects [11,12]. This has led to the hypothesis that the ability to down-regulate inflammatory responses -once parasitaemia is under control -is crucial to avoid immune-mediated pathology, and may therefore be an important feature of clinical immunity to malaria [3,13].…”

“…Moreover, in vitro parasite-induced IFN-g production by PBMC is considerably lower among clinically immune individuals than among semi-immune subjects [11,12]. This has led to the hypothesis that the ability to down-regulate inflammatory responses -once parasitaemia is under control -is crucial to avoid immune-mediated pathology, and may therefore be an important feature of clinical immunity to malaria [3,13].…”