Studies of allogeneic bone marrow and spleen cell transplantation in a murine model using ultraviolet-B light

Abstract

Ultraviolet irradiation inhibits alloreactive and mitogen-induced responses and might reduce both graft-versus-host and host-versus-graft reactions after bone marrow transplantation (BMT). We have studied proliferative responses to mitogens and reactivity in mixed lymphocyte culture after irradiation with ultraviolet (UV)-B light using splenocytes from Balb/c (H-2d) and CBA (H-2k) mice. Response to mitogens and in MLC was strongly inhibited by 20 J/m2 and abolished at 50 J/m2. Clonogenic cell recovery (CFU-GM; CFU-S) after UV-B irradiation was also reduced. When bone marrow and spleen cells were transplanted from parent (Balb/c) animals into F1 hybrid (Balb/c X CBA) recipients, all animals died with features indicative of graft-versus- host disease (GVHD) in 34 days. If the grafts were first irradiated with 100 J/m2 of UV-B at a mean wavelength of 310 nm, then 76% survived to day 80 when they were killed and shown to have normal marrow cellularity. The remainder died in marrow aplasia or of GVHD. H-2 typing in a group of surviving recipients showed either donor hematopoiesis only (8 of 15), mixed allogeneic chimerism (5 of 15), or recipient type hematopoiesis (2 of 15). Higher doses (200 to 300 J/m2) were detrimental to survival with 88% of recipients dying in marrow aplasia. Syngeneic BMT in Balb/c mice showed slower hematopoietic reconstitution when the grafts were first irradiated with 100 J/m2. After BMT from Balb/c to CBA mice all recipients of unirradiated grafts died within 54 days. By contrast, after graft irradiation with 100 J/m2 survival of recipient animals to day 80 was 59%. If these grafts were treated with 50 J/m2 survival was only 26% with an increase in deaths due to GVHD. Hematopoiesis at day 80 in a group of survivors studied by Ig heavy chain allotyping indicated donor type hematopoiesis in 6 of 10 (50 J/m2) and 2 of 9 (100 J/m2). These data indicate that UV-B irradiation inhibits lymphocyte reactivity and can prevent GVHD. However, there is clear in vitro and in vivo evidence of stem cell damage, such that autologous marrow recovery was demonstrated in a proportion of recipients. In parent----F1 UV-irradiated transplants, sustained hematopoietic recovery was effected in the majority by donor stem cells.

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

“…Studies using animal models have further described the dosage effect of UVB light on the development of GVHD. Pamphilon et al 22 used UVB radiation to eliminate GVHD in an F1 hybrid model of GVHD using Balb/c × CBA mice. UVB doses greater than 200 J per cm 2 (20 mJ/cm 2 ) were associated with bone marrow aplasia and death (88%), which are thought to be secondary to the cytocidal effects of UV light on HPCs in high doses, while doses of 10 mJ per cm 2 prolonged graft survival and decreased the occurrence of GVHD.…”

The Role of UV Irradiation in the Prevention of HLA Alloimmunization and in Therapeutic Apheresis.

“…This inability can be non specific, when the recipient is profoundly immunosuppressed, or it can be specific, when the donor, sharing the same histocompatibility antigens, is histocompatible with the recipient, while the recipient possess histocompatibility antigens unknown to the donor. The prevention of bone marrow transplantation-induced GVHD with UV-B irradiation of bone marrow cells has been studied in two types of experimental murine models, haploidentical (Cohn, 1991) and fully allogeneic (Chabot, 1990) (Pamphilon, 1991). In both sets of experiments, there is evidence that UV-B irradiation is deleterious not only to T cells, which mediate GVHD, but also to hematopoietic stem cells.…”