Phenotypic and functional characterization of peripheral blood and bone marrow natural killer cells prior to autologous transplantation.
NK cells can exert potent anti-leukemia activity after either autologous or allogeneic BMT. However, in autologous blood or marrow transplant patients, NK cell number and/or function could be reduced, and also may vary according to the sampling site. In order to evaluate the hypothesis that blood or marrow grafts from autologous transplant patients exhibit impaired NK cell activity that could contribute to disease recurrence, we evaluated the immunologic characteristics of NK cells in the bone marrow (BM) and peripheral blood (PB) from 27 patients undergoing autologous BMT, and also from 20 normal donors. We measured baseline and interleukin-2 (IL-2)-activated NK cell cytotoxicity, as well as expression of IL-2 receptors (IL-2R) (alpha-chain (p55) and beta-chain (p75)), and adhesion molecules. The cytotoxic activity of PB NK cells was significantly lower in autologous transplant patients than in normal donors (P < 0.0005) and this difference was not mitigated following IL-2 activation. In contrast, BM from autologous patients showed normal NK cell cytotoxicity, but contained higher numbers of NK cells (P < 0.025), with more intense CD56 expression (P < 0.05). Expression of p75 was lower on BM than on PB NK cells in both patients and normal donors. In addition, induction of p55 by IL-2 was abrogated in autologous PB NK cells. Therefore, depending on the site of harvest and the nature of donor cells (pre-BMT vs normal), our results show significant differences in NK cell number, function, and IL-2 receptor expression. This may affect relapse rates following autologous transplants performed with either PB or BM grafts.
Arbour
S
S
Division of Hematology-Immunology, Maisonneuve-Rosemont Hospital, Quebec, Canada.
Toupin
S
S
Bélanger
R
R
Gyger
M
M
Hallé
J P
JP
Perreault
C
C
Roy
D C
DC
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood; D002648:Child; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D014182:Transplantation, Autologous
D015815:Cell Adhesion Molecules; D015375:Receptors, Interleukin-2