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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 V β profiles
Author(s) -
Molldrem Jeffrey J.,
Jiang Yin Zheng,
StetlerStevenson Maryalice,
Mavroudis Dimitrios,
Hensel Nancy,
Barrett A. John
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.00920.x
Subject(s) - cd8 , bone marrow , cd3 , immunology , cytopenia , polyclonal antibodies , lymphocyte , biology , myelodysplastic syndromes , medicine , microbiology and biotechnology , antibody , antigen
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 MHC I. TCR Vβ 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 MHC‐I‐restricted suppression of CFU‐GM which are replaced by polyclonal T cells that do not suppress CFU‐GM after ATG treatment.