T-cell ontogeny after autologous bone marrow transplantation: failure to synthesize interleukin-2 (IL-2) and lack of CD2- and CD3-mediated proliferation by both CD4- and CD8+ cells even in the presence of exogeneous IL-2.
T cells generated during a second round of ontogeny after autologous bone marrow transplantation (ABMT) represent a unique model of early T-cell ontogeny in an autologous situation. Since grafted bone marrows were pretreated in vitro with the cyclophosphamide derivative ASTA Z 7557, circulating T cells had to be regenerated from reinfused hematopoietic progenitor cells. The T-cell population derived from 25 patients post-ABMT was phenotypically characterized: an increase in CD8+ cells, a low percentage of CD4+ cells, and a median of 12% CD56+ (NKH1+) cells were found. When the T cells were stimulated with phytohemagglutinin (PHA) and phorbol myristate acetate (PMA), defective interleukin-2 (IL-2) secretion was observed. In addition, proliferative responses of the T cells after activation through the antigen-receptor-dependent CD3 pathway, through the CD2 dependent alternative T-cell pathway, and by the lectin PHA were investigated. Despite the presence of CD2, CD3, alpha/beta chains of the T-cell receptor, and CD25+ IL-2 surface receptors, abnormal proliferative responses were obtained even in the presence of exogeneous IL-2. In experiments where the T-cell population was separated into CD4+ cells and CD8+ cells, both the CD4- and CD8+ subsets were unable to respond to activating and proliferating signals. Thus, T cells at early stages of ontogeny not only possess an intrinsic defect in IL-2 synthesis but, in addition, were unable to express functional IL-2 receptors in response to mitogenic stimuli.
Cayeux
S
S
Department of Internal Medicine, University of Heidelberg, FRG.
Meuer
S
S
Pezzutto
A
A
Körbling
M
M
Haas
R
R
Schulz
R
R
Dörken
B
B
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D000954:Antigens, Surface / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology*; D018801:CD2 Antigens; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016827:CD8 Antigens; D005434:Flow Cytometry; D006410:Hematopoiesis; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors; D014182:Transplantation, Autologous
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic