Dataset Information

Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans.

ABSTRACT:

Background

Immunity to malaria develops naturally in endemic regions, but the protective immune mechanisms are poorly understood. Many vaccination strategies aim to induce T cells against diverse pre-erythrocytic antigens, but correlates of protection in the field have been limited. The objective of this study was to investigate cell-mediated immune correlates of protection in natural malaria. Memory T cells reactive against thrombospondin-related adhesive protein (TRAP) and circumsporozoite (CS) protein, major vaccine candidate antigens, were measured, as were frequencies of CD4(+) CD25(high) T cells, which may suppress immunity, and CD56(+) NK cells and gammadelta T cells, which may be effectors or may modulate immunity.

Methodology and principal findings

112 healthy volunteers living in rural Kenya were entered in the study. Memory T cells reactive against TRAP and CS were measured using a cultured IFNgamma ELISPOT approach, whilst CD4(+) CD25(high) T cells, CD56(+) NK cells, and gammadelta T cells were measured by flow cytometry. We found that T cell responses against TRAP were established early in life (<5 years) in contrast to CS, and cultured ELISPOT memory T cell responses did not correlate with ex-vivo IFNgamma ELISPOT effector responses. Data was examined for associations with risk of clinical malaria for a period of 300 days. Multivariate logistic analysis incorporating age and CS response showed that cultured memory T cell responses against TRAP were associated with a significantly reduced incidence of malaria (p = 0.028). This was not seen for CS responses. Higher numbers of CD4(+) CD25(high) T cells, potentially regulatory T cells, were associated with a significantly increased risk of clinical malaria (p = 0.039).

Conclusions

These data demonstrate a role for central memory T cells in natural malarial immunity and support current vaccination strategies aimed at inducing durable protective T cell responses against the TRAP antigen. They also suggest that CD4(+) CD25(high) T cells may negatively affect naturally acquired malarial immunity.

SUBMITTER: Todryk SM

PROVIDER: S-EPMC2323567 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Publications

Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans.

Todryk Stephen M SM Bejon Philip P Mwangi Tabitha T Plebanski Magdalena M Urban Britta B Marsh Kevin K Hill Adrian V S AV Flanagan Katie L KL

PloS one 20080430 4

<h4>Background</h4>Immunity to malaria develops naturally in endemic regions, but the protective immune mechanisms are poorly understood. Many vaccination strategies aim to induce T cells against diverse pre-erythrocytic antigens, but correlates of protection in the field have been limited. The objective of this study was to investigate cell-mediated immune correlates of protection in natural malaria. Memory T cells reactive against thrombospondin-related adhesive protein (TRAP) and circumsporoz ...[more]

PMID: 18446217

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Dataset Information

Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans.

Background

Methodology and principal findings

Conclusions

Publications

Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans.

Similar Datasets

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