Effects of UVB radiation on cytokine generation, cell adhesion molecules, and cell activation markers in T-lymphocytes and peripheral blood HPCs.

Abstract

Immunomodulatory effects of UV light have increasingly become a focus in transfusion medicine, BMT and transplantation immunology. In the transplant setting, the use of UVB radiation may reduce or abolish T-cell activation without compromising either bone marrow (BM) engraftment or graft-versus-leukemia effect. In this study, BM and apheresis-derived peripheral blood HPCs were used to investigate the effects of UVB on colony-forming ability, CD34+ cell viability, and growth potential, as well as on the secretion of MNC cytokines and the expression of cell surface markers and adhesion molecules. After UVB radiation, enriched populations of T cells and antigen-presenting cells (APCs) were treated with PHA, and the MNC response was measured, as was colony-forming ability. CD34+ cells were quantified and their growth potential was determined in culture. Next, T-cell activation status, cell adhesion molecule and cell surface activation marker expression, and cytokine profiles were evaluated, and cytokine mRNA was quantitated. Parallel studies were done in unirradiated control cell populations. Low-dose (10 mJ/cm(2)) UVB mitigates MNC proliferative responses by 94 percent while maintaining 60 and 80 percent of colony-forming ability in peripheral blood HPC and BM preparations, respectively, and >50 percent of colony-forming ability in CD34+ cell-enriched samples. Low-dose UVB radiation also significantly reduces T-cell production of TNFalpha, TNFalpha mRNA, TNFbeta, IL-2, and IL-6 and downregulates T-cell expression of CD28, CD25, CD69, and intercellular adhesion molecule 1. These findings have shown that a "window" of low-dose UVB radiation (10 mJ/cm(2)) exists, at which BM- and peripheral blood-derived MNC proliferation is inactivated, while the HPCs are relatively spared. UVB light selectively affects T cells, while APCs are resistant to low doses of UVB. UVB radiation also alters the expression of some cell surface markers and cytokines that are important in T-cell activation pathways. Reduction of T-cell activation without cytocidal effect may allow UVB radiation to become an immunomodulating agent in BM or HPC transplantation.