[Lymphokine-induced suppression of erythropoiesis by normal T lymphocytes and retrovirus-associated lymphoproliferative disease].
Activation of genes for interleukin 2 (IL2) and its receptor by the tat gene product of the human retrovirus HTLV-I has been linked to the pathogenesis of adult T cell leukemia. In earlier studies we have demonstrated that IL2-induced inhibition of erythropoiesis is mediated by activated T-Lymphocytes expressing the IL2-receptor. We have now examined the role of activated T cells and interferon-gamma (IF gamma) in inhibition of normal erythropoiesis and in HTLV-I associated lymphoproliferative disease. T cells were activated by triggering of the antigen receptor complex with CD3 monoclonal antibody. Incubation with CD5 antibody recognizing a T cell epitope distinct from the antigen receptor served as a control. Supernatants derived from CD3 activated T cells generated in the presence of IL2 caused a dose-dependent suppression of erythropoiesis. Treatment of supernatant interferon-gamma neutralizing antibody caused a greater than 95% abrogation of inhibition. Next we investigated the mechanisms for acquired pure red cell aplasia in a patient with T gamma-lymphoproliferative disease (T gamma-LPD). Patient marrow erythroid progenitors were 17 +/- 9% of control and increased to 88-102% of control following marrow T cell depletion. Myeloid progenitors were normal. Patient suppressor T cells inhibited growth of autologous and allogeneic marrow erythroid but not myeloid progenitors and produced high titers of IF gamma. The inhibitory factor in patient T cell supernatant was acid labile and sensitive to trypsin, consistent with properties of IF gamma. Prior depletion of activated T cells abrogated the suppressive effect of patient T cell-derived supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)
Burdach
S
S
Zentrum für Kinderheilkunde, Medizinische Einrichfungen, Universität Düsseldorf.
Levitt
L
L
Wahn
V
V
Göbel
U
U
D000741:Anemia, Aplastic / Q000175:diagnosis* / Q000235:genetics; D004920:Erythropoiesis; D005786:Gene Expression Regulation; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D007376:Interleukin-2; D012367:RNA, Viral; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma
Lymphokin-vermittelte Suppression der Erythropoese durch normale T-Lymphozyten und bei Retrovirus-assoziierter lymphoproliferativer Erkrankung.