Deficient T cell granulocyte-macrophage colony stimulating factor production in allogeneic bone marrow transplant recipients.
The proliferation and differentiation of donor hematopoietic progenitor cells in bone marrow transplantation (BMT) recipients is influenced by hematopoietic growth factors, which could derive from either T cells or adherent stromal bone marrow cells, or both. In this study of 20 BMT recipients, we asked whether T lymphocytes arising from donor bone marrow grafts were able to express normal levels of granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA, and to secrete normal levels of soluble GM-CSF in response to the mitogen phytohemagglutinin. We have found that T cells obtained up to 18 months following BMT express little or no PHA-induced GM-CSF message. T cell GM-CSF secretion in response to PHA is also reduced or absent. This T cell GM-CSF defect was observed in all patients studied, whether or not donor bone marrows had undergone T cell depletion. This defect likely reflects a broader deficit in mitogen-induced lymphokine production. This defect likely contributes to BMT recipients' blunted responses to infections, and contributes to graft failure in T cell-depleted transplants.
Thomas
S
S
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
Clark
S C
SC
Rappeport
J M
JM
Nathan
D G
DG
Emerson
S G
SG
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D007377:Interleukin-3 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism* / Q000637:transplantation
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor