Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans.
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-04-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2323567?pdf=render |
| _version_ | 1818203923127730176 |
|---|---|
| author | Stephen M Todryk Philip Bejon Tabitha Mwangi Magdalena Plebanski Britta Urban Kevin Marsh Adrian V S Hill Katie L Flanagan |
| author_facet | Stephen M Todryk Philip Bejon Tabitha Mwangi Magdalena Plebanski Britta Urban Kevin Marsh Adrian V S Hill Katie L Flanagan |
| author_sort | Stephen M Todryk |
| collection | DOAJ |
| description | 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.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).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. |
| first_indexed | 2024-12-12T03:33:03Z |
| format | Article |
| id | doaj.art-21bce570dae648a2ac26e2ad78225765 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T03:33:03Z |
| publishDate | 2008-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-21bce570dae648a2ac26e2ad782257652022-12-22T00:39:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-04-0134e202710.1371/journal.pone.0002027Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans.Stephen M TodrykPhilip BejonTabitha MwangiMagdalena PlebanskiBritta UrbanKevin MarshAdrian V S HillKatie L FlanaganImmunity 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.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).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.http://europepmc.org/articles/PMC2323567?pdf=render |
| spellingShingle | Stephen M Todryk Philip Bejon Tabitha Mwangi Magdalena Plebanski Britta Urban Kevin Marsh Adrian V S Hill Katie L Flanagan Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans. PLoS ONE |
| title | Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans. |
| title_full | Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans. |
| title_fullStr | Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans. |
| title_full_unstemmed | Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans. |
| title_short | Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans. |
| title_sort | correlation of memory t cell responses against trap with protection from clinical malaria and cd4 cd25 high t cells with susceptibility in kenyans |
| url | http://europepmc.org/articles/PMC2323567?pdf=render |
| work_keys_str_mv | AT stephenmtodryk correlationofmemorytcellresponsesagainsttrapwithprotectionfromclinicalmalariaandcd4cd25hightcellswithsusceptibilityinkenyans AT philipbejon correlationofmemorytcellresponsesagainsttrapwithprotectionfromclinicalmalariaandcd4cd25hightcellswithsusceptibilityinkenyans AT tabithamwangi correlationofmemorytcellresponsesagainsttrapwithprotectionfromclinicalmalariaandcd4cd25hightcellswithsusceptibilityinkenyans AT magdalenaplebanski correlationofmemorytcellresponsesagainsttrapwithprotectionfromclinicalmalariaandcd4cd25hightcellswithsusceptibilityinkenyans AT brittaurban correlationofmemorytcellresponsesagainsttrapwithprotectionfromclinicalmalariaandcd4cd25hightcellswithsusceptibilityinkenyans AT kevinmarsh correlationofmemorytcellresponsesagainsttrapwithprotectionfromclinicalmalariaandcd4cd25hightcellswithsusceptibilityinkenyans AT adrianvshill correlationofmemorytcellresponsesagainsttrapwithprotectionfromclinicalmalariaandcd4cd25hightcellswithsusceptibilityinkenyans AT katielflanagan correlationofmemorytcellresponsesagainsttrapwithprotectionfromclinicalmalariaandcd4cd25hightcellswithsusceptibilityinkenyans |