Hyper IgE in stimulatory graft-versus-host disease: role of interleukin-4.
Intravenous injection of 2 x 10(8) DBA/2 spleen cells into adult intact (C57BL/6 x DBA/2) F1 mice results in a stimulatory graft-versus-host reaction (GVHR) linked to the recognition by donor CD4+ T cells of Ia alloantigens on host B cells. In the experiments presented here, we found that this GVHR is associated with a major increase in IgE serum levels which was already present 7 days after the cell transfer. At 6 weeks, mean IgE levels were more than 200-fold above the control values. Host B cells were responsible for the hypersecretion of IgE in stimulatory GVHR since it was also observed when the DBA/2 donor inoculum was depleted of B cells but not when the F1 recipients were irradiated. The induction of IgE secretion required donor CD4+ T cells as treatment of the donor inoculum with lytic anti-CD4 monoclonal antibody (MoAb) completely prevented the occurrence of the hyper IgE whereas depletion of CD8+ cells had no influence on this parameter. The role played by interleukin-4 (IL-4) in this model was analysed in vivo by the administration of the 11B11 anti-IL-4 rat MoAb (total dose 36 mg) during the first 12 days following induction of stimulatory GVHR by 8 x 10(7) DBA/2 spleen cells. This treatment completely prevented the development of hyper IgE whereas the administration of a control rat MoAb had no significant effect. We conclude that stimulatory GVHR in mice is associated with a major increase in serum IgE which is mediated by IL-4.
Doutrelepont
J M
JM
Department of Nephrology, Hôpital Erasme, Brussels, Belgium.
Moser
M
M
Leo
O
O
Abramowicz
D
D
Vanderhaegen
M L
ML
Urbain
J
J
Goldman
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology*; D007073:Immunoglobulin E / Q000378:metabolism*; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000637:transplantation
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015847:Interleukin-4; D007073:Immunoglobulin E