PMID- 15034567
OWN - NLM
STAT- MEDLINE
DCOM- 20040608
LR  - 20061115
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 10
IP  - 4
DP  - 2004 Apr
TI  - A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite 
      protein correlates with protection from natural Plasmodium falciparum infection 
      and disease.
PG  - 406-10
AB  - Many human T-cell responses specific for epitopes in Plasmodium falciparum have 
      been described, but none has yet been shown to be predictive of protection 
      against natural malaria infection. Here we report a peptide-specific T-cell assay 
      that is strongly associated with protection of humans in The Gambia, West Africa, 
      from both malaria infection and disease. The assay detects 
      interferon-gamma-secreting CD4(+) T cells specific for a conserved sequence from 
      the circumsporozoite protein, which binds to many human leukocyte antigen 
      (HLA)-DR types. The correlation was observed using a cultured, rather than an ex 
      vivo, ELISPOT assay that measures central memory-'type T cells rather than 
      activated effector T cells. These findings provide direct evidence for a 
      protective role for CD4(+) T cells in humans, and a precise target for the design 
      of improved vaccines against P. falciparum.
FAU - Reece, William H H
AU  - Reece WH
AD  - Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, 
      Oxford OX3 9DU, UK.
FAU - Pinder, Margaret
AU  - Pinder M
FAU - Gothard, Philip K
AU  - Gothard PK
FAU - Milligan, Paul
AU  - Milligan P
FAU - Bojang, Kalifa
AU  - Bojang K
FAU - Doherty, Tom
AU  - Doherty T
FAU - Plebanski, Magdalena
AU  - Plebanski M
FAU - Akinwunmi, Peter
AU  - Akinwunmi P
FAU - Everaere, Simone
AU  - Everaere S
FAU - Watkins, Katherine R
AU  - Watkins KR
FAU - Voss, Gerald
AU  - Voss G
FAU - Tornieporth, Nadia
AU  - Tornieporth N
FAU - Alloueche, Ali
AU  - Alloueche A
FAU - Greenwood, Brian M
AU  - Greenwood BM
FAU - Kester, Kent E
AU  - Kester KE
FAU - McAdam, Keith P W J
AU  - McAdam KP
FAU - Cohen, Joe
AU  - Cohen J
FAU - Hill, Adrian V S
AU  - Hill AV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040314
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Epitopes)
RN  - 0 (Protozoan Proteins)
RN  - 0 (circumsporozoite protein, Protozoan)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Amino Acid Sequence
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Conserved Sequence
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitopes/*immunology
MH  - Humans
MH  - Immunologic Memory
MH  - Malaria, Falciparum/immunology/*prevention & control
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Protozoan Proteins/*immunology
EDAT- 2004/03/23 05:00
MHDA- 2004/06/21 10:00
CRDT- 2004/03/23 05:00
PHST- 2004/01/20 00:00 [received]
PHST- 2004/02/26 00:00 [accepted]
PHST- 2004/03/23 05:00 [pubmed]
PHST- 2004/06/21 10:00 [medline]
PHST- 2004/03/23 05:00 [entrez]
AID - nm1009 [pii]
AID - 10.1038/nm1009 [doi]
PST - ppublish
SO  - Nat Med. 2004 Apr;10(4):406-10. doi: 10.1038/nm1009. Epub 2004 Mar 14.