HLA-C Matching Status Does Not Affect Rituximab-Mediated Antibody-Dependent Cellular Cytotoxicity by Allogeneic Natural Killer Cells.
Summary of "HLA-C Matching Status Does Not Affect Rituximab-Mediated Antibody-Dependent Cellular Cytotoxicity by Allogeneic Natural Killer Cells."
Risk of leukemia relapse after T cell-depleted hematopoietic stem cell transplantation is lower in the "HLA-C mismatched" recipient-donor combinations. This might be attributable to increased natural killing by allogeneic NK cells carrying a KIR that does not bind to HLA-C on target cells (HLA-C-uncoupled KIR). Considering a new strategy of allogeneic NK cell transfer with rituximab to treat B-cell lymphomas, however, it is unknown whether the HLA-C matching status also affects rituximab-mediated antibody-dependent cellular cytotoxicity (ADCC). To address this issue, we investigated the levels of ADCC by purified NK cells carrying an HLA-C-uncoupled KIR, where the NK cell donors had either matched or mismatched HLA-C combination with target cells. Purified NK cells carrying an HLA-C-uncoupled KIR consistently showed enhanced ADCC against target cells when NK cell donors had an HLA-C-mismatch. When NK cell donors did not have an HLA-C mismatch, it was inconsistent whether HLA-C-uncoupled KIR caused ADCC enhancement. When the levels of ADCC by whole NK cells were compared, there were substantial differences among the donors regardless of the HLA-C matching status. Subjects with HLA-C mismatch may not have an advantage when cytoimmunotherapy using allogeneic NK cells is considered in combination with rituximab.
Affiliation
Department of Hematology, University of Tsukuba , Tsukuba , Japan.
Journal Details
This article was published in the following journal.
Name: Immunological investigations
ISSN: 1532-4311
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22676066
- DOI: http://dx.doi.org/10.3109/08820139.2012.691148
Medical and Biotech [MESH] Definitions
Antibody-dependent Cell Cytotoxicity
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
Immunity, Cellular
Those manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
Immunity, Humoral
Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION.
Coombs' Test
Hemagglutination test in which Coombs' reagent (antiglobulin, or anti-human globulin rabbit immune serum) is added to detect incomplete (non-agglutinating, univalent, blocking) antibodies coating erythrocytes. The direct test is applied to red cells which have been coated with antibody in vivo (e.g., in hemolytic disease of newborn, autoimmune hemolytic anemia, and transfusion reactions). The indirect test is applied to serum to detect the presence of antibody (e.g., in detection of incompatibility in cross-matching tests, detection and identification of irregular antibodies, and in detection of antibodies not identifiable by other means).
Immune Adherence Reaction
A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
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