Allosuppressor and allohelper T cells in acute and chronic graft-vs-host disease. I. Alloreactive suppressor cells rather than killer T cells appear to be the decisive effector cells in lethal graft-vs.-host disease.
Splenic T cells from B10 donors were injected into irradiated (B10 x DBA/2)F1 mice. Either 5 or 6 d later, activated donor T cells were recovered from the spleens of these primary F1 (1 degree F1) recipients and transferred to groups of nonirradiated syngeneic F1 (2 degrees F1) recipients. Whereas day-5-activated parental T cells induced the characteristic symptoms of acute graft-vs.-host disease (GVHD) and eventually lethal GVHD, day-6-activated B10 T cells failed to induce acute GVHD but induced symptoms of chronic GVHD. Interestingly, the inability of day-6-activated T cells to induce lethal GVHD could not be ascribed to a lack in anti-F1 T killer cells. The combined results of functional studies indicated that day-6 cells were enriched for alloreactive helper T cells, whereas day-5 cells were enriched for alloreactive suppressor cells. Hence, our findings indicate that acute GVHD and lethal GVHD are caused by alloreactive donor T suppressor but not T killer cells, and that symptoms of chronic GVHD are caused by alloreactive donor T helper cells.
D000208:Acute Disease; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic; D004920:Erythropoiesis; D005260:Female; D005630:Fructans / Q000276:immunology; D006087:Graft vs Host Reaction; D007074:Immunoglobulin G / Q000096:biosynthesis; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000166:cytology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009026:Mortality; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors
D005630:Fructans; D007074:Immunoglobulin G