Immunosuppression and lymphoid hypoplasia associated with chronic graft versus host disease is dependent upon IFN-gamma production.
We have previously shown that both IFN-gamma and IFN-beta are produced in vivo and in vitro by spleen cells obtained from mice experiencing a chronic form of graft vs host disease (GVHD). Further, we have shown that in vitro production of IFN-beta by spleen cells from GVHD mice may play a role in the suppressed in vitro mitogen responsiveness of these cells. This study was undertaken to investigate if treatment of such mice with mAb to IFN-gamma or IFN-beta could alter the immunosuppression or lymphoid hypoplasia associated with chronic GVHD. GVHD was induced across minor histocompatibilities by the i.v. injection of B10.D2 spleen cells into sublethally irradiated BALB/c mice. These mice were given daily injections for 20 days of one of the following: 1) mAb to IFN-gamma, 2) mAb to IFN-beta, or 3) control IgG. Histologic examination of these mice at 21 to 22 days post transplantation revealed that mice treated with mAb to IFN-beta or control IgG had dramatic hypoplasia of the thymus, spleen, and lymph nodes which was similar to untreated GVHD mice. Mice given mAb to IFN-gamma, however, had no lymphoid hypoplasia and had a near normal gross and histologic appearance of their thymus, spleen, and lymph node tissue when compared with syngeneic controls. In vitro mitogen-induced proliferative responses of spleen and lymph node cells obtained from GVHD mice or GVHD mice treated with mAb to IFN-beta were severely suppressed or absent. In contrast, spleen and lymph node cells from GVHD mice given mAb to IFN-gamma were capable of giving a significant in vitro proliferative response to Con A, PHA, and LPS. Further, natural suppressor cell activity and spontaneous production of IFN-beta, a characteristic of this form of GVHD, was absent in spleen cells obtained from GVHD mice treated with mAb to IFN-gamma. These results further identify the IFN as playing critical roles in the pathogenesis of GVHD.
Klimpel
G R
GR
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
Annable
C R
CR
Cleveland
M G
MG
Jerrells
T R
TR
Patterson
J C
JC
D000818:Animals; D002908:Chronic Disease; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology*; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
D007370:Interferon Type I; D007371:Interferon-gamma