IL2 activated killer cells may contribute to cytomegalovirus induced marrow hypoplasia after bone marrow transplantation.
Cytomegalovirus (CMV) infection remains the commonest cause of infective death following allogeneic bone marrow transplantation (BMT). CMV disease post-BMT occurs in the context of compromised cellular defence mechanisms and is associated with marrow hypoplasia and pneumonitis. However, CMV infection induces release of interleukin 2 (IL2) which in turn generates MHC unrestricted lymphokine activated killer (LAK) cells. We have investigated whether recruitment of IL2 activated MHC unrestricted defence mechanisms post-transplant can be implicated in the marrow hypoplasia that frequently accompanies CMV infection. The results show that IL2 activated peripheral blood mononuclear cells (PBMC) have substantial cytotoxicity against MHC matched and MHC mismatched marrow fibroblasts but that this activity is not specific for CMV infected fibroblasts; uninfected target cells are also equally killed. Furthermore, post-BMT PBMC show greater responsiveness to IL2 than normal PBMC in killing of marrow fibroblasts. We provide a hypothesis from these observations which may explain some of the consequences of CMV infection post-BMT. Local production of IL2 activated cytotoxic cells which would be generated during CMV infection would damage uninfected as well as infected marrow fibroblasts and thereby could compromise haemopoietic growth factor production by marrow fibroblasts. Similarly generated cytotoxicity in the lung may accompany CMV pneumonitis. Our results suggest that administration of anti-IL2 receptor antibody may have a therapeutic role in CMV disease post-BMT as has recently been shown in graft-versus-host disease.
Duncombe
A S
AS
Department of Haematology, Royal Free Hospital, London UK.
Grundy
J E
JE
Prentice
H G
HG
Brenner
M K
MK
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000502:physiology / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002648:Child; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D008285:Major Histocompatibility Complex; D009000:Monocytes / Q000378:metabolism; D011024:Pneumonia, Viral / Q000209:etiology* / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000276:immunology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2