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A unique population of effector memory lymphocytes identified by CD146 having a distinct immunophenotypic and genomic
Mohamed F Elshal1, Sameena S Khan, Nalini Raghavachari
1Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. melshal2002@yahoo.com
Insights
CD146 identifies unique T and B lymphocyte subsets in circulation. These CD146+ lymphocytes exhibit effector memory traits and may be primed for endothelial adhesion and extravasation to inflammation sites.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD146 is an adhesion molecule on endothelial cells.
- CD146 expression on lymphocytes is poorly understood.
- This study characterizes CD146+ lymphocytes in healthy donors.
Purpose of the Study:
- To characterize CD146+ lymphocytes in peripheral circulation.
- To investigate the function and phenotype of CD146+ lymphocytes.
Main Methods:
- Immunophenotyping of lymphocytes from healthy donors.
- In vitro induction and upregulation of CD146 expression.
- Gene profiling of CD146+ and CD146- T cells.
- Assessing lymphocyte adherence to endothelial monolayers.
Main Results:
- CD146 is expressed on low percentages of circulating T, B, and NK cells.
- CD146 expression on T and B cells can be upregulated in vitro.
- CD146+ T cells display effector memory phenotype (low CCR7, CD45RA) and enhanced endothelial adherence.
- Upregulation of IL-8 and genes involved in cell adhesion and signaling in CD146+ T cells.
Conclusions:
- CD146 identifies distinct T and B lymphocyte populations in circulation.
- CD146+ T cells possess effector memory characteristics.
- These cells may be primed for endothelial adhesion and migration to inflammatory sites.
Background:
CD146 is a well described homotypic adhesion molecule found on endothelial cells and a limited number of other cell types. In cells from the peripheral circulation, CD146 has also been reported to be on activated lymphocytes in vitro and in vivo. The function associated with CD146 expression on lymphoid cells is unknown and very little information is available concerning the nature of CD146+ lymphocytes. In the current study, lymphocytes from healthy donors were characterized based upon the presence or absence of CD146 expression.
Results:
CD146 was expressed on a low percentage of circulating T lymphocytes, B lymphocytes, and NK cells in healthy individuals. CD146 expression can be induced and upregulated in vitro on both B cells and T cells, but does not correlate with the expression of other markers of T cell activation. CD146 positive T cells do not represent clonal expansions as determined with the use of anti Vbeta reagents. Data suggest that CD146 positive cells have enhanced adherence to endothelial monolayers in vitro. Gene profiling and immunophenotyping studies between CD146+ and CD146- T cells revealed several striking genotypic distinctions such as the upregulation of IL-8 and phenotypic differences including the paucity of CCR7 and CD45RA among CD146 positive T cells, consistent with effector memory function. A number of genes involved in cell adhesion, signal transduction, and cell communication are dramatically upregulated in CD146+ T cells compared to CD146- T cells.
Conclusion:
CD146 appears to identify small, unique populations of T as well as B lymphocytes in the circulation. The T cells have immunophenotypic characteristics of effector memory lymphocytes. The characteristics of these CD146+ lymphocytes in the circulation, together with the known functions in cell adhesion of CD146 on endothelial cells, suggests that these lymphocytes may represent a small subpopulation of cells primed to adhere to the endothelium and possibly extravasate to sites of inflammation.
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