Mechanism of the anti-GVHD effect of IL-2. I. Protective host-type cell populations are not induced by IL-2 treatment alone.
We have recently demonstrated that high-dose IL-2 administered for a short period (2.5 days) beginning on the day of bone marrow transplantation mediates a marked protective effect against GVHD in mice, while preserving the ability to achieve alloengraftment (1). This protective effect is augmented by administration of T cell-depleted (TCD) syngeneic marrow, and is dependent upon early administration of IL-2 (1). The graft-vs-tumor effect against the EL4 leukemia/lymphoma is not diminished in animals protected from GVHD by IL-2 (2). In an attempt to determine whether or not IL-2-activated host-type cells might be responsible for GVHD protection, we have now performed adoptive transfer studies. The results failed to provide evidence that treatment of lethally irradiated mice with IL-2 activates protective host-derived or syngeneic marrow-derived cell populations which can be adoptively transferred to lethally irradiated secondary recipients receiving allogeneic GVHD-producing inocula. Likewise, treatment of lethally irradiated mice with a complete 2.5-day course of IL-2 prior to administration of allogeneic inocula did not lead to GVHD protection. These results suggest that either IL-2 directly inhibits the GVH reactivity of allogeneic GVH-reactive cells, or that GVH reactivity is attenuated by IL-2 during the period of interaction of donor- and host-type cells.
Abraham
V S
VS
Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Sykes
M
M
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014184:Transplantation, Homologous
D007376:Interleukin-2