Haematological response of patients with myelodysplastic syndrome to antithymocyte globulin is associated with a loss of lymphocyte-mediated inhibition of CFU-GM and alterations in T-cell receptor Vbeta profiles.
We have demonstrated that 44% of myelodysplastic syndrome (MDS) patients with cytopenia have a haematological response to antithymocyte globulin (ATG). Three ATG responders and two non-responders with refractory anaemia were further studied for lymphocyte-mediated inhibition of bone marrow using a standard CFU-GM assay. In responders, peripheral blood lymphocytes (PBL) added at a 5:1 ratio suppressed CFU-GM by 54+/-9% (P=0.04) and was reversed by ATG treatment. Pre-treatment marrow depleted of CD3 lymphocytes, increased CFU-GM by 32% (P=0.02) in an ATG responder, but not in a non-responder. CD3 lymphocytes from 6-month post-treatment marrow did not inhibit pre-treatment CFU-GM, indicating ATG had affected the T cells. Pre-treatment marrow depleted of CD8 lymphocytes, increased CFU-GM by 60% (P=0.01) and 49% (P=0.03) in two ATG responders, but not in a non-responder. Inhibition required cell-cell interaction through MHCI. TCRVbeta families, analysed by SSCP, changed from clonal to polyclonal in one ATG responder after 6 months, but clones persisted in a non-responder. These results indicate patients with refractory anaemia who respond to ATG have CD8 T-cell clones that mediate MHCI-restricted suppression of CFU-GM which are replaced by polyclonal T cells that do not suppress CFU-GM after ATG treatment.
Molldrem
J J
JJ
Department of Blood and Marrow Transplantation, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Jiang
Y Z
YZ
Stetler-Stevenson
M
M
Mavroudis
D
D
Hensel
N
N
Barrett
A J
AJ
D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003114:Colony-Forming Units Assay; D005260:Female; D006801:Humans; D008231:Lymphopenia / Q000276:immunology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000961:Antilymphocyte Serum; D011948:Receptors, Antigen, T-Cell