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CD16- CD56+ natural killer cells after bone marrow transplantation
R Jacobs1, M Stoll, G Stratmann
1Abt. für Klinische Immunologie und Transfusionsmedizin, Medizinische Hochschule Hannover, Germany.
Insights
Natural killer (NK) cells reconstitute after bone marrow transplant, with CD56+bright cells appearing in 35% of patients. These cells, distinct from typical NK cells, show unique activation markers and altered cytotoxicity, impacting immune reconstitution and cytokine therapy.
Area of Science:
- Immunology
- Hematology
Background:
- Natural killer (NK) cells are lymphocytes defined by CD56 expression and typically CD16, while lacking CD3.
- A rare subset of NK cells (CD3-, CD16-, CD56+) exists in healthy individuals, comprising <2% of peripheral blood lymphocytes.
Purpose of the Study:
- To analyze the reconstitution of immune system subsets in patients post-bone marrow transplantation.
- To characterize the distinct NK cell populations, CD56+dim and CD56+bright, observed during immune reconstitution.
Main Methods:
- Analysis of 70 patients undergoing autologous or allogeneic bone marrow transplantation.
- Flow cytometry to identify and quantify NK cell subsets (CD56+dim, CD56+bright) and their associated markers (CD3, CD16, IL-2R, CD2R, CD26).
- Assessment of NK cell and antibody-dependent cellular cytotoxicity (ADCC) activity, with and without IL-2 and interferon gamma stimulation.
Main Results:
- Two distinct NK cell subsets, CD56+dim and CD56+bright, were observed in 35% of patients at a mean of 4 months post-transplant.
- CD56+bright cells, a CD3- CD16- subset, reached frequencies up to 70% of NK cells and 40% of lymphocytes post-transplant.
- CD56+bright cells expressed IL-2R, CD2R, and CD26, lacked CD16, and had lower baseline cytotoxicity but enhanced activity upon IL-2/interferon gamma stimulation compared to CD56+dim cells.
Conclusions:
- The emergence of CD56+bright NK cells during immune reconstitution suggests distinct activation or differentiation pathways.
- These subsets may play a crucial role in the recovery of immune function after transplantation.
- The differential response of NK cell subsets to IL-2 highlights their potential importance in post-transplant cytokine therapy.
Abstract:
Natural killer (NK) cells are phenotypically defined as lymphocytes expressing the antigens CD56 and mostly CD16 (Fc gamma RIII), but lacking CD3. A small CD3- CD16- CD56+ NK cell subset has been described in normal individuals representing less than 2% of peripheral blood lymphocytes. We analyzed here 70 patients for their reconstitution of the immune system during follow-up after autologous or allogeneic bone marrow transplantation. In 35% of these patients, two different NK cell subsets, namely CD56+dim and CD56+bright cells, were observed. The mean duration of these two subsets after transplant was 4 months. Sixty-five percent of the patients exhibited an increased number of NK cells, but only the typical CD16+ CD56+dim population. The CD56+bright subpopulation represented a particular CD3- CD16- NK subset, with posttransplant frequencies up to 70% of all NK cells and 40% of peripheral blood lymphocytes, respectively. In contrast to normal CD56+dim NK cells, CD56+bright cells coexpressed the activation antigens p75 beta-chain of interleukin-2 receptor (IL-2R), CD2R, and CD26, but were negative for CD16. NK and antibody-dependent cellular cytotoxicity activity of CD56+bright cells was low compared with CD56+dim NK cells. But using IL-2 and interferon gamma, their cytotoxicity could be enhanced even more than in CD56+dim lymphocytes. These different subsets may reflect distinct activation or differentiation steps of NK cells during reconstitution of the immune system. Their differential response to IL-2 may be of functional importance for posttransplant cytokine therapy.