Alterations in T cell-derived colony-stimulating factors associated with GVH-induced immune deficiency.
Injection of parental C57BL/10 spleen cells into unirradiated immune-competent (B10 x B10.BR)F1 hosts has been demonstrated to produce a graft-vs.-host-induced immune deficiency in T cell-mediated functions, including mitogen or alloantigen stimulated proliferation or cytotoxic T cell generation. The production of T cell-derived lymphokines affecting hematopoiesis was also altered during GVH. During the first two weeks of GVH, IL-3 and particularly GM-CSF were produced spontaneously; in subsequent weeks, the spontaneous production dropped to normal or subnormal levels. CSF content in concanavalin A-stimulated splenic supernatants was reduced at weeks 1-2, and declined to less than 5% of normal levels by 3-4 weeks of GVH. This decline in CSF content was correlated with a decrease in immune function as assessed by concanavalin A-stimulated IL-2 production and by generation of cytotoxic T lymphocytes. Concurrent with the recovery of immune function during GVH weeks 8-15, mitogen-stimulated production of CSF returned to normal levels. In addition to the decrease in CSF production identified in acute suppressive GVH, CSF content in concanavalin A-stimulated splenic supernatants was also decreased in chronic stimulatory GVH, generated in the strain combination (B6 x B6bm1)F1----(B6bm1 x B6bm12)F1. This decrease in CSF production correlated with a decrease in self-restricted T helper cell function. Finally, a decrease in both immune function and CSF production capacity was observed in the acute GVH following allogeneic (minor histocompatibility loci) bone marrow transplantation into irradiated hosts.
Hakim
F T
FT
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Pluznik
D H
DH
Shearer
G M
GM
D000818:Animals; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006087:Graft vs Host Reaction / Q000276:immunology* / Q000528:radiation effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D011833:Radiation Injuries, Experimental / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007376:Interleukin-2; D007377:Interleukin-3; D003208:Concanavalin A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor