Inhibition of graft-vs-host induced immunodeficiency with immunosuppressive therapy.
The pathologic features of the acute graft-vs-host disease occurring in unirradiated (C57Bl/6 X A/J)F1 mice injected intravenously with lymphocytes from the C57Bl/6 parent are similar to those reported for other parental----F1 hybrid combinations. When stimulated in culture with concanavalin A, lipopolysaccharide or alloantigen, spleen cells from B6AF1 mice that had been injected 11 days previously with B6 lymphocytes exhibited proliferative responses that were drastically reduced in comparison to the responses of spleen cells from F1 hosts injected with syngeneic lymphocytes. IL2 production in GVH spleen cell cultures was also diminished. Proliferative responses and IL2 production were partially restored in mice given immunosuppressive therapy with azathioprine, cyclosporin A or Sch 24937 a drug whose inhibitory effects on cellular and humoral immune responses in mice have recently been described. Phenotypic analyses by flow cytometry of the GVH splenocyte population indicated that the most consistent change in the GVH spleen was the appearance of an Lyt2+ L3T4+ T cell subset which in the majority of experiments was accompanied by an increase in cells expressing only the Lyt2 antigen. Both subpopulations were reduced in mice that had recovered immunological responsiveness following immunosuppressive therapy. The results suggest that in this GVH model the development of an immunodeficient state is directly related to the induction of an active T suppressor cell population and that such cells are effectively eliminated from the splenocyte population following treatment with some immunosuppressive drugs.
Smith
S R
SR
Department of Inflammation, Schering Corporation, Bloomfield, NJ 07003.
Pennline
K
K
Terminelli
C
C
DaFonseca
M
M
Pellerito
F
F
Umland
S
S
D000284:Administration, Oral; D000818:Animals; D001379:Azathioprine / Q000494:pharmacology; D002469:Cell Separation; D003520:Cyclophosphamide / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D005434:Flow Cytometry; D006087:Graft vs Host Reaction / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D007211:Indoles; D007376:Interleukin-2; D011725:Pyridines; C054872:Sch 24937; D003520:Cyclophosphamide; D001379:Azathioprine