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Deconvoluting post-transplant immunity: cell subset-specific mapping reveals pathways for activation and expansion of memory T, monocytes and B cells
- Source :
- PLoS ONE, Vol 5, Iss 10, p e13358 (2010), PLoS ONE
- Publication Year :
- 2010
- Publisher :
- Public Library of Science (PLoS), 2010.
-
Abstract
- A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO(+)CD62L(-) effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes
Male
Surgery/Transplantation
Immunology/Innate Immunity
lcsh:Medicine
Pathology/Immunology
Biology
Monocytes
Blood cell
Immunology/Leukocyte Signaling and Gene Expression
03 medical and health sciences
0302 clinical medicine
Immune system
Antigen
Antigens, CD
Transplantation Immunology
Immunity
medicine
Humans
Cytotoxic T cell
lcsh:Science
Aged
Oligonucleotide Array Sequence Analysis
030304 developmental biology
B-Lymphocytes
0303 health sciences
Multidisciplinary
Genetics and Genomics/Functional Genomics
lcsh:R
Genetics and Genomics/Gene Expression
Middle Aged
Kidney Transplantation
Genetics and Genomics/Gene Function
Gene expression profiling
medicine.anatomical_structure
Immunology/Leukocyte Activation
Immunology/Immune Response
Immunology
Immunology/Antigen Processing and Recognition
Female
lcsh:Q
Immunologic Memory
Cytometry
CD8
Research Article
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....c7597d0868b78fdd90715e5b94a8b589