Limits...
Characterization of CD8+ T cell differentiation following SIVΔnef vaccination by transcription factor expression profiling.

Billingsley JM, Rajakumar PA, Connole MA, Salisch NC, Adnan S, Kuzmichev YV, Hong HS, Reeves RK, Kang HJ, Li W, Li Q, Haase AT, Johnson RP - PLoS Pathog. (2015)

Bottom Line: The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8+ T cell responses induced by SIVΔnef.Expression of transcription factors associated with effector differentiation, such as ID2 and RUNX3, were decreased over time, while expression of transcription factors associated with quiescence or memory differentiation, such as TCF7, BCOR and EOMES, increased.These data suggest transcription factor expression profiling is a novel method that can provide additional data complementary to the analysis of memory cell differentiation based on classical phenotypic markers.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, United States of America; Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.

ABSTRACT
The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8+ T cell responses induced by SIVΔnef. As a novel approach to characterize cell differentiation following vaccination, we used multi-target qPCR to measure transcription factor expression in naïve and memory subsets of CD8++ T cells, and in SIV-specific CD8+ T cells obtained from SIVΔnef-vaccinated or wild type SIVmac239-infected macaques. Unsupervised clustering of expression profiles organized naïve and memory CD8+ T cells into groups concordant with cell surface phenotype. Transcription factor expression patterns in SIV-specific CD8+ T cells in SIVΔnef-vaccinated animals were distinct from those observed in purified CD8+ T cell subsets obtained from naïve animals, and were intermediate to expression profiles of purified central memory and effector memory T cells. Expression of transcription factors elicited by SIVΔnef vaccination also varied over time: cells obtained at later time points, temporally associated with greater protection, appeared more central-memory like than cells obtained at earlier time points, which appeared more effector memory-like. Expression of transcription factors associated with effector differentiation, such as ID2 and RUNX3, were decreased over time, while expression of transcription factors associated with quiescence or memory differentiation, such as TCF7, BCOR and EOMES, increased. CD8+ T cells specific for a more conserved epitope expressed higher levels of TBX21 and BATF, and appeared more effector-like than cells specific for an escaped epitope, consistent with continued activation by replicating vaccine virus. These data suggest transcription factor expression profiling is a novel method that can provide additional data complementary to the analysis of memory cell differentiation based on classical phenotypic markers. Additionally, these data support the hypothesis that ongoing stimulation by SIVΔnef promotes a distinct protective balance of CD8+ T cell differentiation and activation states.

No MeSH data available.


Related in: MedlinePlus

Principal component analysis of transcription factor expression profiles from SIV-specific MHC tetramer-sorted CD8+ T cells from animals vaccinated with SIVΔnef, animals infected with wild-type SIV, and sorted CD8+ T cell subsets.Plot of principal components 1 and 2 for each of the expression profiles assessed from sorted naïve and memory CD8+ T cell subsets, SIV-specific MHC tetramer-sorted CD8+ T cells isolated from SIVΔnef-vaccinated animals, and MHC tetramer-sorted CD8+ T cells isolated from animals (n = 5) at 20 weeks following wild-type SIV infection. Principal components 1 and 2 explain 77 percent of cumulative total variance.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4358830&req=5

ppat.1004740.g004: Principal component analysis of transcription factor expression profiles from SIV-specific MHC tetramer-sorted CD8+ T cells from animals vaccinated with SIVΔnef, animals infected with wild-type SIV, and sorted CD8+ T cell subsets.Plot of principal components 1 and 2 for each of the expression profiles assessed from sorted naïve and memory CD8+ T cell subsets, SIV-specific MHC tetramer-sorted CD8+ T cells isolated from SIVΔnef-vaccinated animals, and MHC tetramer-sorted CD8+ T cells isolated from animals (n = 5) at 20 weeks following wild-type SIV infection. Principal components 1 and 2 explain 77 percent of cumulative total variance.

Mentions: A plot of principal components 1 and 2 (Fig. 4) positioned Gag CM9-specific cells obtained from wild-type SIV-infected animals near the sorted effector memory cells but with higher PC2 values. Tat SL8-specific cells from wild-type SIV-infected animals were more heterogeneous but generally occupied positions more positive along the PC2 axis than SIVΔnef-induced cells, with PC2 values similar to sorted effector memory cells. These results are consistent with the idea that ongoing activation by replicating virus may induce a more effector-like phenotype, and that epitope escape facilitates a more central memory-like phenotype.


Characterization of CD8+ T cell differentiation following SIVΔnef vaccination by transcription factor expression profiling.

Billingsley JM, Rajakumar PA, Connole MA, Salisch NC, Adnan S, Kuzmichev YV, Hong HS, Reeves RK, Kang HJ, Li W, Li Q, Haase AT, Johnson RP - PLoS Pathog. (2015)

Principal component analysis of transcription factor expression profiles from SIV-specific MHC tetramer-sorted CD8+ T cells from animals vaccinated with SIVΔnef, animals infected with wild-type SIV, and sorted CD8+ T cell subsets.Plot of principal components 1 and 2 for each of the expression profiles assessed from sorted naïve and memory CD8+ T cell subsets, SIV-specific MHC tetramer-sorted CD8+ T cells isolated from SIVΔnef-vaccinated animals, and MHC tetramer-sorted CD8+ T cells isolated from animals (n = 5) at 20 weeks following wild-type SIV infection. Principal components 1 and 2 explain 77 percent of cumulative total variance.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358830&req=5

ppat.1004740.g004: Principal component analysis of transcription factor expression profiles from SIV-specific MHC tetramer-sorted CD8+ T cells from animals vaccinated with SIVΔnef, animals infected with wild-type SIV, and sorted CD8+ T cell subsets.Plot of principal components 1 and 2 for each of the expression profiles assessed from sorted naïve and memory CD8+ T cell subsets, SIV-specific MHC tetramer-sorted CD8+ T cells isolated from SIVΔnef-vaccinated animals, and MHC tetramer-sorted CD8+ T cells isolated from animals (n = 5) at 20 weeks following wild-type SIV infection. Principal components 1 and 2 explain 77 percent of cumulative total variance.
Mentions: A plot of principal components 1 and 2 (Fig. 4) positioned Gag CM9-specific cells obtained from wild-type SIV-infected animals near the sorted effector memory cells but with higher PC2 values. Tat SL8-specific cells from wild-type SIV-infected animals were more heterogeneous but generally occupied positions more positive along the PC2 axis than SIVΔnef-induced cells, with PC2 values similar to sorted effector memory cells. These results are consistent with the idea that ongoing activation by replicating virus may induce a more effector-like phenotype, and that epitope escape facilitates a more central memory-like phenotype.

Bottom Line: The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8+ T cell responses induced by SIVΔnef.Expression of transcription factors associated with effector differentiation, such as ID2 and RUNX3, were decreased over time, while expression of transcription factors associated with quiescence or memory differentiation, such as TCF7, BCOR and EOMES, increased.These data suggest transcription factor expression profiling is a novel method that can provide additional data complementary to the analysis of memory cell differentiation based on classical phenotypic markers.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, United States of America; Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.

ABSTRACT
The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8+ T cell responses induced by SIVΔnef. As a novel approach to characterize cell differentiation following vaccination, we used multi-target qPCR to measure transcription factor expression in naïve and memory subsets of CD8++ T cells, and in SIV-specific CD8+ T cells obtained from SIVΔnef-vaccinated or wild type SIVmac239-infected macaques. Unsupervised clustering of expression profiles organized naïve and memory CD8+ T cells into groups concordant with cell surface phenotype. Transcription factor expression patterns in SIV-specific CD8+ T cells in SIVΔnef-vaccinated animals were distinct from those observed in purified CD8+ T cell subsets obtained from naïve animals, and were intermediate to expression profiles of purified central memory and effector memory T cells. Expression of transcription factors elicited by SIVΔnef vaccination also varied over time: cells obtained at later time points, temporally associated with greater protection, appeared more central-memory like than cells obtained at earlier time points, which appeared more effector memory-like. Expression of transcription factors associated with effector differentiation, such as ID2 and RUNX3, were decreased over time, while expression of transcription factors associated with quiescence or memory differentiation, such as TCF7, BCOR and EOMES, increased. CD8+ T cells specific for a more conserved epitope expressed higher levels of TBX21 and BATF, and appeared more effector-like than cells specific for an escaped epitope, consistent with continued activation by replicating vaccine virus. These data suggest transcription factor expression profiling is a novel method that can provide additional data complementary to the analysis of memory cell differentiation based on classical phenotypic markers. Additionally, these data support the hypothesis that ongoing stimulation by SIVΔnef promotes a distinct protective balance of CD8+ T cell differentiation and activation states.

No MeSH data available.


Related in: MedlinePlus