Open AccessPRESERVATION OF LYMPHOKINE-ACTIVATED KILLER ACTIVITY FOLLOWING T CELL DEPLETION OF HUMAN BONE MARROW
Author(s) -
William R. Drobyski,
Victoria D. Piaskowski,
Robert C. Ash,
James T. Casper,
Robert L. Truitt
Publication year - 1990
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/00007890-199010000-00020
Subject(s) - lymphokine activated killer cell , bone marrow , immunology , lymphokine , interleukin 2 , t cell , natural killer cell , t lymphocyte , cd3 , leukemia , population , biology , interleukin 21 , cancer research , medicine , immune system , cytotoxic t cell , in vitro , cd8 , biochemistry , environmental health
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.