In vitro narrowband UVB phototherapy of murine lymphocytes preferentially depletes CD8+T cells in both young and aged mice
Veenstra J, Lim H, Gibson H. In vitro narrowband UVB phototherapy of murine lymphocytes preferentially depletes CD8+T cells in both young and aged mice. Journal of the American Academy of Dermatology 2018; 79(3 Suppl 1):AB164.
Journal of the American Academy of Dermatology
Phototherapy use in dermatology is largely empirical as many of the proposed mechanisms have yet to be fully elucidated. Much of the current data suggest phototherapy operates primarily via immunosuppression, which is further strengthened by the fact that the vast majority of photoresponsive dermatoses respond similarly well to immunosuppressive drugs. It is currently unclear what acute impact narrowband UVB (NB-UVB) treatment has on specific lymphocyte populations and if these subsets are differentially affected. Furthermore, it is uncertain if there is any differential response based on the age of subject. To address these questions, we harvested fresh splenocytes from BALB/c mice 4 and 12 months of age, resuspended the cells in tissue culture medium and treated with NB-UVB (from 0-500 mJ/cm2) using a Daavlin 1 series NB-UVB panel. Approximately 20 hours later cellular viability was assessed and flow cytometry was performed to quantitate the following lymphocyte populations: Total T cells, CD4+ T cells, CD8+ T cells, FoxP3+ T regulatory cells (Tregs), B cells, and natural killer (NK) cells. No substantial differences in lymphocyte population percentages were noted between splenocytes taken from mice 4 and 12 months of age. Total lymphocyte viability declined by ;10% at 100 mJ/cm2 and _20% at 500 mJ/cm2. No substantial changes in total B cells, NK cells, or CD4+ T-cell populations were observed, however CD8+ T cells were found to have a ;30% and 50% population decline at 250 and 500 mJ/cm2, respectively. Tregs also showed a population decline (25% at 500 mJ/cm2), with natural Tregs (nTregs, defined by coexpression of FoxP3 and Neuropilin-1) more strikingly affected (55% decline at 500 mJ/cm2). These results indicate acute NBUVB exposure preferentially depletes CD8+ T cells and Tregs without significantly impacting viability of other lymphocyte populations. This CD8+ selective depletion is in accordance with previous studies finding decreased levels of interferon gamma producing T cells after treatment with phototherapy. Future studies will evaluate acute and chronic changes in various lymphocyte populations, including molecular alterations that may contribute toward an immune stimulatory versus tolerant phenotype. A more comprehensive understanding of these mechanisms will support incorporation of novel adjunctive therapy to NB-UVB to improve efficacy and potentially enable reduced dosing and/or less frequent phototherapy.
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