Protective Immunity Induced with the RTS,S-AS Vaccine Is Associated with IL-2 and TNF-α Producing Effector and Central Memory CD4 T CellsReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Joanne M. Lumsden , Robert J. Schwenk , Lisa E. Rein, Philippe Moris, Michel Janssens, Opokua Ofori-Anyinam, Joe Cohen, Kent E. K

Fuente: http://plos.srce.hr/



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