Quantitative assessment of posttransplant host-specific interleukin-2-secreting T-helper cell precursors in patients with and without acute graft-versus-host disease after allogeneic HLA-identical sibling bone marrow transplantation.
نویسندگان
چکیده
Recent studies in mice and humans have emphasized an important contribution of host-reactive minor histocompatibility antigen (mH)-specific lymphokine-secreting donor T-helper cells (Th) for the induction of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). By using limiting dilution (LD) and clonal specificity analyses, we investigated in 14 patients with and without acute GVHD after non-T-depleted HLA-identical sibling BMT whether posttransplant host-reactive mH-specific interleukin-2 (IL-2)-secreting Th are involved in the development of clinically significant acute GVHD and the establishment of tolerance. At different time intervals posttransplant (I, days 0 through 45; II, days 45 through 90; III, days 90 through 180), host-specific IL-2-secreting Th-precursors (Th-p) were quantitatively assessed in six patients during clinically apparent grade II-III acute GVHD. Frequencies of responding Th-p ranged from 1/13,000 to 1 4,000. The presence of host-specific Th-p was significantly correlated with the development of grade II-III acute GVHD (P = .0003 by Fisher's exact test). The detectability of host-specific Th-p preceded the clinical onset of grade II-III acute GVHD. Host-specific Th-p were no longer detectable after the clinical resolution of grade II-III acute GVHD. No subsequent chronic GVHD was observed in these patients. However, prolonged occurrence of host-specific Th-p was accompanied by clinically persisting acute GVHD and the onset of secondary chronic GVHD. In patients with no acute GVHD (grade 0) (n = 7) and grade I (n = 1) acute GVHD, host-specific Th-p were not detectable at all. We conclude that host-reactive Th are critically involved in the development and maintenance of acute GVHD and may contribute to the establishment of tolerance after genotypically HLA-identical sibling BMT.
منابع مشابه
Pretransplant Detection of Human Minor Histocompatibility Antigen-Specific Naive and Memory Interleukin-2-Secreting T Cells Within Class I Major Histocompatibility Complex (MHC)-Restricted CD8 + and Class I1 MHC-Restricted CD4+ T-cel l Subsets
Recent studies have shown that host-reactive interleukin2 (IL-2)-secreting donor T lymphocytes (TI) are critically involved in the development of acute graft-versus-host disease (GVHD) after allogeneic HLA-identical sibling bone marrow transplantation (BMT). To further characterize the responding TI, we determined the frequency of pretransplant IL-2-secreting TI-precursors (TI-p) between eight ...
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ورودعنوان ژورنال:
- Blood
دوره 81 3 شماره
صفحات -
تاریخ انتشار 1993