Consequences of the photodynamic treatment of resting and activated peripheral T lymphocytes

The impact of the immunomodulatory photosensitizer benzoporphyrin derivativ e monoacid ring A (BPD-MA, verteporfin) and visible light on the survival a nd surface receptor pattern of resting and activated murine T cells was eva luated. T cells treated for 48 h with immobilized anti-CD3 monoclonal antib ody upregulated expression of the interleukin-2 receptor alpha-chain (CD25) , transferrin receptor (CD71), the apoptosis-regulating Fas receptor (CD95) , contained a greater level of the anti-apoptotic protein Bcl-2 and accumul ated significantly more BPD-MA than their unactivated counterparts. Activat ed T cells displayed a modestly greater susceptibility to the photodynamic induction of DNA fragmentation than resting T tells. Resting T cells treate d with sub-lethal levels of BPD-MA and light did not exhibit changes in sur face levels of CD3, CD4, CD8, CD28, CD45 or T cell receptor (TCR) beta-chai n structures. However, levels of major histocompatibility complex (MHC) cla ss I antigens were decreased while the density of Thy-1.2 (CD90) increased on these cells. Photodynamically treated T cells failed to express optimal CD25 levels when exposed to the mitogenic anti-CD3 antibody. Activated T ce lls treated with sub-lethal levels of BPD-MA and light exhibited lower CD25 levels, a temporary block in cell cycle transition, but unaltered expressi on of MHC Class I, CD3, CD4, CD8, CD45, CD54, CD71, CD122 (IL-2R beta-chain ) or TCR beta-chain antigens 24 h afterward. Resting and activated T lympho cytes differ in susceptibility to PDT-mediated apoptosis but both types are sensitive to anti-proliferative effects the treatment exerts at sub-lethal photosensitizer levels. The marked sensitivity of activated T cells to pho todynamic inactivation likely contributes to the immunomodulatory action of BPD-MA. (C) 1999 Elsevier Science B.V. All rights reserved.