NDLI: Protective Immunity Induced with the RTS,S/AS Vaccine Is Associated with IL-2 and TNF-α Producing Effector and Central Memory CD4+ T Cells

Content Provider	PubMed Central
Author	Lumsden, Joanne M. Schwenk, Robert J. Rein, Lisa E. Moris, Philippe Janssens, Michel Ofori-anyinam, Opokua Cohen, Joe Kester, Kent E. Heppner, D. Gray Krzych, Urszula
Editor	Derya, Unutmaz
Copyright Year	2011
Abstract	A phase 2a RTS,S/AS malaria vaccine trial, conducted previously at the Walter Reed Army Institute of Research, conferred sterile immunity against a primary challenge with infectious sporozoites in 40% of the 80 subjects enrolled in the study. The frequency of Plasmodium falciparum circumsporozoite protein (CSP)-specific CD4+ T cells was significantly higher in protected subjects as compared to non-protected subjects. Intrigued by these unique vaccine-related correlates of protection, in the present study we asked whether RTS,S also induced effector/effector memory (TE/EM) and/or central memory (TCM) CD4+ T cells and whether one or both of these sub-populations is the primary source of cytokine production. We showed for the first time that PBMC from malaria-non-exposed RTS,S-immunized subjects contain both TE/EM and TCM cells that generate strong IL-2 responses following re-stimulation in vitro with CSP peptides. Moreover, both the frequencies and the total numbers of IL-2-producing CD4+ TE/EM cells and of CD4+ TCM cells from protected subjects were significantly higher than those from non-protected subjects. We also demonstrated for the first time that there is a strong association between the frequency of CSP peptide-reactive CD4+ T cells producing IL-2 and the titers of CSP-specific antibodies in the same individual, suggesting that IL-2 may be acting as a growth factor for follicular Th cells and/or B cells. The frequencies of CSP peptide-reactive, TNF-α-producing CD4+ TE/EM cells and of CD4+ TE/EM cells secreting both IL-2 and TNF-α were also shown to be higher in protected vs. non-protected individuals. We have, therefore, demonstrated that in addition to TNF-α, IL-2 is also a significant contributing factor to RTS,S/AS vaccine induced immunity and that both TE/EM and TCM cells are major producers of IL-2.
Related Links	http://dx.doi.org/10.1371/journal.pone.0020775
Starting Page	20775
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	7
Volume Number	6
Language	English
Publisher	Public Library of Science
Publisher Date	2011-07-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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