PROLONGED SKIN ALLOGRAFT SURVIVAL AFTER PHOTODYNAMIC THERAPY ASSOCIATED WITH MODIFICATION OF DONOR SKIN ANTIGENICITY

Background. The ability to prolong graft survival, in some cases by de pleting donor antigen-presenting cells (APCs), and the subsequent demo nstration that lymphocytes stimulated by non-APCs become anergic, sugg ested that graft survival and tolerance induction might be achieved by manipulating donor APCs to render them incompetent. This possibility was tested in histoincompatible murine skin allograft with photodynami c therapy (PDT). Methods. Skin sections (C57BL/6) were exposed in vitr o to low doses of benzoporphyrin derivative monoacid ring A (BPD) (ver teporfin) and light (lambda=690+/-10 nm; low-dose PDT) before implanta tion on recipients (BALB/c). Furthermore, the effect of the treatment on the surface molecules of donor-derived Langerhans cells (LC) was ev aluated by fluorescence-activate d cell sorter analysis; the effect of treatment on the LC alloreactivity in the mixed epidermal cell. lymph ocyte reaction was also evaluated. Results. Pretreating skin to be gra fted with low-dose PDT can significantly prolong the survival of allog rafts from 9.3+/-2.2 (n=42) days (control group) to 16.9+/-1.7 days (n =20; treated group). Moreover, low-dose PDT significantly down-regulat ed the major histocompatibility complex and costimulatory (B7) molecul es (60-90% reduction) on LC, but not LC-specific endocytic receptor (D EC-205), CD45, intercellulr adhesion molecule 1, LC viabilities, and e ctophosphatase activity on LC. Additionally, this treatment significan tly suppressed the ability of LC to stimulate alloreactive T cells to proliferate. Conclusions. Since engaging T cell receptors in the absen ce of costimulation results in suboptimal activation of T cells and ul timately anergy, it appears that the immunomodulatory effects of low-d ose PDT associated with extended engraftment may depend upon decreased LC expression of major histocompatibility complex and costimulatory m olecules.