Preservation of lymphokine-activated killer activity following T cell depletion of human bone marrow.
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.
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
W R
WR
Drobyski
V
V
Piaskowski
R C
RC
Ash
J T
JT
Casper
R L
RL
Truitt
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001853:Bone Marrow / Q000276:immunology*; D016026:Bone Marrow Transplantation; D017252:CD3 Complex; D019002:CD56 Antigen; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D007938:Leukemia / Q000601:surgery; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019002:CD56 Antigen; C062279:CD6 antigen; D011948:Receptors, Antigen, T-Cell