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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

Differential expression of transcription factors in CD8+ naïve and memory T cell subsets.log2 mean expression values were normalized to naïve cell samples.
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ppat.1004740.g002: Differential expression of transcription factors in CD8+ naïve and memory T cell subsets.log2 mean expression values were normalized to naïve cell samples.

Mentions: Distinct sets of transcription factors displayed unique expression profiles among cell subsets (Fig. 2). The Wnt pathway effectors LEF1 and TCF were expressed at the highest levels in naïve and central memory cells, and lower levels in transitional and effector memory cells. The transcription factors TBX21, PRDM1 and NFIL3, were expressed at the highest levels in effector memory cells. In contrast, EOMES, AHR and RORC, were expressed at the highest level in transitional memory cells.


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)

Differential expression of transcription factors in CD8+ naïve and memory T cell subsets.log2 mean expression values were normalized to naïve cell samples.
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1004740.g002: Differential expression of transcription factors in CD8+ naïve and memory T cell subsets.log2 mean expression values were normalized to naïve cell samples.
Mentions: Distinct sets of transcription factors displayed unique expression profiles among cell subsets (Fig. 2). The Wnt pathway effectors LEF1 and TCF were expressed at the highest levels in naïve and central memory cells, and lower levels in transitional and effector memory cells. The transcription factors TBX21, PRDM1 and NFIL3, were expressed at the highest levels in effector memory cells. In contrast, EOMES, AHR and RORC, were expressed at the highest level in transitional memory cells.

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