Preservation of lymphokine-activated killer activity following T cell depletion of human bone marrow. Transplantation 1990 Oct;50(4):625-32
Date
10/01/1990Pubmed ID
1699309DOI
10.1097/00007890-199010000-00020Scopus ID
2-s2.0-0025001706 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
T cell depletion has decreased the incidence and severity of graft-versus-host disease following transplantation of allogeneic bone marrow. In the treatment of leukemia, decreased GVHD has often been associated with diminished antileukemia or graft-versus-leukemia (GVL) reactivity resulting in higher relapse rates. However, we have not seen a loss of the GVL effect following transplantation of marrow grafts depleted of CD3+ T cells. This suggests that non-T-cell effectors may play a role in preventing leukemic relapse. To study whether natural killer and lymphokine-activated killer (LAK) activity in BM was compromised by T cell depletion, the effect of T-cell-specific monoclonal antibodies against CD3 and CD6 determinants alone, or in combination, on the generation and expansion of NK/LAK cells was examined in vitro and compared to the effect of T depletion on mitogen-driven T cell proliferation. Limiting dilution analysis revealed that T depletion with CD3 and/or CD6 specific antibodies significantly reduced the number of proliferating T lymphocytes but did not significantly affect the frequency of cells able to expand and mediate LAK activity. Bone marrow, depleted of CD3+ or CD6+ T cells, generated levels of LAK activity equivalent to non-T-cell-depleted bone marrow following long-term culture in recombinant interleukin 2. CD3- NKH-1+ cells were the predominant population in rIL-2 expanded marrow cultures prior to transplant and in the peripheral blood of patients who had received a CD3-depleted marrow graft 21-65 days earlier. These studies show that it is possible to selectively reduce GVH-reactive T cells in allogeneic bone marrow while retaining non-T-effector cells with potential to mediate an antileukemia effect in vivo.
Author List
Drobyski WR, Piaskowski V, Ash RC, Casper JT, Truitt RLAuthor
William R. Drobyski MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antigens, CDAntigens, Differentiation, T-Lymphocyte
Bone Marrow
Bone Marrow Transplantation
CD3 Complex
CD56 Antigen
Graft vs Host Disease
Humans
Killer Cells, Lymphokine-Activated
Killer Cells, Natural
Leukemia
Lymphocyte Activation
Lymphocyte Depletion
Receptors, Antigen, T-Cell
T-Lymphocyte Subsets
T-Lymphocytes