T lymphocyte repopulation and differentiation after bone marrow transplantation. Early shifts in the ratio between T4+ and T8+ T lymphocytes correlate with the occurrence of acute graft-versus-host disease

Abstract

Acute graft-versus-host disease (GVHD), a major complication of allogeneic bone marrow transplantation (BMT), is probably mediated by T lymphocytes present in the marrow graft. In this study, the repopulation of the peripheral blood with T4+ and T8+ T cells was investigated during the period preceding the occurrence of acute GVHD. Twenty-four allogeneic and 11 autologous BMT recipients were monitored from day 4 post-BMT onward by the use of monoclonal antibodies, indirect immunofluorescence, and flow cytometry. The recipients of allogeneic transplants received methotrexate as GVHD prophylaxis. Similar recovery patterns for T4+ and T8+ T cells were found following autologous and allogeneic BMT. However, lymphoid repopulation occurred at a clearly faster rate after autologous BMT. T4+ T cells were the first to reappear in the peripheral blood, followed by T8+ T cells 4–7 days later. The T8+ T cell reconstitution occurred at an even faster rate in patients who were to develop grade II-IV GVHD, as compared with those with grade O-I GVHD, thus leading to an earlier decrease in the T4/T8 ratio. Of 10 patients with a T4/T8 ratio less than 2.5 at day 19, 9 developed grade II-IV GVHD and 1 showed no GVHD. Of 14 patients with a ratio greater than 2.5 at that time, only 2 developed grade II-IV and 12 grade O-I GVHD (p less than 0.001). In the 11 patients developing grade II-IV GVHD, the T4/T8 ratio decreased to values less than 2.5 before the first clinical symptoms of GVHD in 9; it coincided in one and occurred later in another patient. Thus, early monitoring of the T4/T8 ratio can distinguish patients at risk of developing grade II-IV GVHD.

Translational Mini-Review Series on B cell subsets in disease. Reconstitution after haematopoietic stem cell transplantation – revelation of B cell developmental pathways and lineage phenotypes

“…Cells of the adaptive immune system form slower than innate cells after HSCT, and functional deficiencies can be detected years after normal numbers of cells are reached [3,4]. As the numbers of CD8 + T cells increase earlier than CD4 + T cells, the CD4/CD8 ratio is initially reversed [9]. This early expansion is dependent on homeostatic peripheral proliferation of memory T cells, both of rare recipient-derived T cells surviving the conditioning regimen and of donorderived co-transferred T cells, rather than from thymic production [10,11].…”

Bone Marrow Transplantation in the Rat

“…Blood lymphopenia and granulocytosis have already been recorded in human bone marrow recipients [7] and so has the finding that regeneration of wbitc cells in tbe blood is similar in the syngeneic compared with the allogeneic recipient [12|. It is noteworthy, however, that the proportions of blast cells, LGL.…”