Functional depletion of T cells by vincristine and methylprednisolone as an in vitro model for the prevention of graft versus host disease.
BACKGROUND AND METHODS. The outcome of mismatched bone marrow transplantation is still severely hampered by graft versus host disease (GVHD) and graft rejection. Procedures for the recognition and selective elimination of T cells are still unsatisfactory due to the increased incidence of graft failure and late rejection. Lymphocyte proliferation and generation of cytotoxic T cells (CTL) in response to allogeneic cells are considered good in vitro correlates of GVHD and have been used in the present study to asses the capacity of two drugs (vincristine, VCR, and methylprednisolone, MP) to affect the T cells involved in these reactions. RESULTS AND CONCLUSION. Treatment in vitro with VCR and MP has been shown to inhibit the functional capacity of peripheral blood lymphocytes to proliferate (mean reduction 95.8%) and to generate CTL in response to haploidentical stimulator cells. Responsiveness to antigens and mitogens was affected to a minor extent (mean reduction 40% and 65.5%, respectively), and the method allowed recovery of hemopoietic precursors. The results suggest that treatment of donor bone marrow with VCR and MP is worth studying as a new approach to the prevention of GVHD in haploidentical bone marrow transplantation.
Lanfranchi
A
A
Cattedra di Chimica Applicata alle Scienze Biomediche, Facoltà di Medicina e Chirurgia, Università, Italy.
Andolina
M
M
Tettoni
K
K
Porta
F
F
Locatelli
F
F
De Manzini
A
A
Candotti
F
F
Albertini
A
A
D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens / Q000032:analysis*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D008775:Methylprednisolone / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*; D014750:Vincristine / Q000494:pharmacology*
D006680:HLA Antigens; D014750:Vincristine; D008775:Methylprednisolone