Cd4 T Cell Activation as a Predictor for Treatment Failure in Ugandans With Plasmodium Falciparum Malaria

Eggena, Mark; Hopkins, Heidi; Barugahare, Banson; Okello, Martin; Ssali, Francis; Mugyenyi, Peter; Rosenthal, Philip J.; Cao, Huyen; Dorsey, Grant

doi:10.4269/ajtmh.2006.74.41

Cited by 3 publications

(3 citation statements)

References 17 publications

(24 reference statements)

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“…Acute malaria infection may also be associated with an enhanced cellular activation state. Co-expression of CD38/HLA-DR on T cell subsets has previously been studied in both HIV-1/AIDS or malaria alone (Hunt et al 2003, Eggena et al 2006, Naniche et al 2011) and immune activation was considered a predictor of treatment failure in malaria patients (Eggena et al 2006). Malaria infection can present with a pro-inflammatory response and cytokine imbalance (Ayimba et al 2011, Davenport et al 2012.…”

Section: Discussionmentioning

confidence: 99%

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

Chavale

Santos-Oliveira²,

Da‐Cruz³

et al. 2012

Mem. Inst. Oswaldo Cruz

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Section: Discussionmentioning

confidence: 99%

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

Chavale

Santos-Oliveira²,

Da‐Cruz³

et al. 2012

Mem. Inst. Oswaldo Cruz

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“…The expression of activation markers provides a general assessment of the extent to which a pathogen activates the immune system (Eggena et al 2006). In the present study, we evaluated the expression levels of CCR5, CD25, and CD95 on CD4+ T cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Characterization of peripheral blood T lymphocyte subsets in Chinese rhesus macaques with repeated or long-term infection with Plasmodium cynomolgi

Ruan

Zhang

et al. 2011

Parasitol Res

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T lymphocytes play a vital role in antimalaria immunity, but there is little information about the role of T cells in malaria infection. In order to explore the profile of T cells in malaria immunity, we infected Chinese rhesus macaques with the malaria parasite (Plasmodium cynomolgi) and examined the dynamics of T cell subsets. Both repeated and long-term infections were involved. Our results showed that the monkeys in the repeated infection group acquired protective immunity through primary infection, which was evidenced by a much lower parasitemia, milder anemia, and milder fever during reinfection; the monkeys in the long-term infection group also developed protective immunity, but this was not sufficient to eliminate the parasite. The total counts of leukocytes, neutrophils, CD3+ T cells, CD4+ or CD8+ T cells, and naïve and memory CD4+ and CD8+ T cells declined during the acute phase of malaria but increased after the parasite was controlled. The total number of activated CD4+ T cells significantly increased during malaria in animals with a long-term infection, which remained at least 3 months after the termination of malaria. However, the activated CD4+ T cells decreased during the acute phase of infection in the repeated infection group and converted to preinfection levels after malaria was cured. Regulatory CD4+ T cells continued to increase during the malaria infections and quickly reverted to preinfection levels after the parasite was controlled. Our study provides a systematic analysis of the kinetic profiles of T lymphocyte subsets during malaria infections and provides some experimental insight into malaria immunology.

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“…In CHMI studies, we have shown that the control of the parasite in malaria‐naïve volunteers following the infection with P. falciparum ‐infected red blood cells (pRBCs) is associated with the expansion of a population of CD4 + T cells co‐expressing the activation marker CD38 8 . However, in naturally exposed individuals from Uganda, an increased frequency of CD38‐expressing CD4 + T cells predicts treatment failure 9 , and in another study, CD38 + CD4 + T‐cell frequency correlated positively with HIV viral load, which was further accentuated in patients co‐infected with malaria 10 .…”

Section: Introductionmentioning

confidence: 99%

A population of CD4^hiCD38^hi T cells correlates with disease severity in patients with acute malaria

et al. 2020

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Objective CD4+ T cells are critical mediators of immunity to Plasmodium spp. infection, but their characteristics during malarial episodes and immunopathology in naturally infected adults are poorly defined. Flow cytometric analysis of PBMCs from patients with either P. falciparum or P. knowlesi malaria revealed a pronounced population of CD4+ T cells co‐expressing very high levels of CD4 and CD38 we have termed CD4hiCD38hi T cells. We set out to gain insight into the function of these novel cells. Methods CD4+ T cells from 18 patients with P. falciparum or P. knowlesi malaria were assessed by flow cytometry and sorted into populations of CD4hiCD38hi or CD4norm T cells. Gene expression in the sorted populations was assessed by qPCR and NanoString. Results CD4hiCD38hi T cells expressed high levels of CD4 mRNA and canonical type 1 regulatory T‐cell (TR1) genes including IL10, IFNG, LAG3 and HAVCR2 (TIM3), and other genes with relevance to cell migration and immunomodulation. These cells increased in proportion to malaria disease severity and were absent after parasite clearance with antimalarials. Conclusion In naturally infected adults with acute malaria, a prominent population of type 1 regulatory T cells arises that can be defined by high co‐expression of CD4 and CD38 (CD4hiCD38hi) and that correlates with disease severity in patients with falciparum malaria. This study provides fundamental insights into T‐cell biology, including the first evidence that CD4 expression is modulated at the mRNA level. These findings have important implications for understanding the balance between immunity and immunopathology during malaria.

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Cd4 T Cell Activation as a Predictor for Treatment Failure in Ugandans With Plasmodium Falciparum Malaria

Cited by 3 publications

References 17 publications

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

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

Characterization of peripheral blood T lymphocyte subsets in Chinese rhesus macaques with repeated or long-term infection with Plasmodium cynomolgi

A population of CD4^hiCD38^hi T cells correlates with disease severity in patients with acute malaria

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Cd4 T Cell Activation as a Predictor for Treatment Failure in Ugandans With Plasmodium Falciparum Malaria

Cited by 3 publications

References 17 publications

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

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

Characterization of peripheral blood T lymphocyte subsets in Chinese rhesus macaques with repeated or long-term infection with Plasmodium cynomolgi

A population of CD4hiCD38hi T cells correlates with disease severity in patients with acute malaria

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A population of CD4^hiCD38^hi T cells correlates with disease severity in patients with acute malaria