Am J Blood Res 2011;1(2):110-118
Original Article
Visualization of immune response kinetics in full allogeneic chimeras
Gregory Elkin, Tatyana B. Prigozhina, Shimon Slavin, Olga Gurevitch, Sofia Khitrin, Igor B. Resnick
Department of Bone Marrow Transplantation, Hadassah Hebrew University Medical Center, P.O.B. 12000, Jerusalem 91120,
Israel; The International Center for Cell Therapy and Cancer, Tel Aviv Sourasky Medical Center, 14 Weizman Street, Tel Aviv
64239, Israel
Received June 5, 2011; accepted July 27, 2011; Epub August 22, 2011; published September 30, 2011
Abstract: Background. Donor Lymphocyte Infusion (DLI) is a well-recognized tool for augmentation of the anti-leukemia effect
after mismatched bone marrow transplantation. Experimental results show, however, that DLI efficacy is strongly dependent
on the number of donor hematopoietic cells persisting in recipient after transplantation. It is strong in mixed chimeras and
relatively weak in full chimeras (FC) that replace host antigen-presenting cells by donor antigen-presenting cells. In this study
we applied a new in vivo cytotoxicity monitoring method for evaluation of the changes in FC anti-host immunity after co-
transplantation of donor and host hematopoietic cells together. Method. Full hematopoietic chimeras and naïve control mice
were transplanted with a mixture of equivalent numbers of donor and recipient or donor and third party splenocytes labeled by
a cell-permeable fluorescent dye CFDA-SE. The animals were sacrificed at various time points, and their splenocyte
suspensions were prepared, depleted of red blood cells, stained with allophycocyanin-labeled anti-H2b antibodies, and
analyzed using fluorescence-activated cell sorting. The immune response was assessed according to the percentage of
single positive CFDA-SE+/ H2b- cells of all CFDA-SE+ cells. Results. FC grafted with splenocytes from similar FC mixed with
splenocytes from naïve host-type or third-party-type mice rejected host cells within 14 days, and third-party cells within 7 days.
NK cell depletion in vivo had no influence on host cell rejection kinetics. Co-infusion of host–type splenocytes with splenocytes
obtained from naïve donor-type mice resulted in significant acceleration of host cell rejection (10 days). Naïve mice rejected
the same amount of allogeneic lymphocytes within 3 days. Conclusions. Proposed method provides a simple and sensitive
tool to evaluate in vivo post-transplant cytotoxicity in different experimental settings. The method demonstrates that FC are
specifically deficient in their ability to reject host lymphocytes even when antigen-presenting host cells are provided. DLI
improve anti-host immune response in FC but can not restore it to the level observed in naïve donor-type mice.
(AJBR1106001).
Keywords: Transplantation, chimerism, immune response, leukemia, donor lymphocyte infusion
Full Text PDF
Address all correspondence to:
Igor B. Resnick, MD
Department of Bone Marrow Transplantation
Hadassah Hebrew University Medical Center, P.O.B. 12000,
91120, Jerusalem, Israel
E-mail: gashka@hadassah.org.il
Tel: 972-2-677-8353;
Fax: 972-2-642-2731
Igor B. Resnick: gashka@hadassah.org.il
Original Article
Visualization of immune response kinetics in full allogeneic chimeras
Gregory Elkin, Tatyana B. Prigozhina, Shimon Slavin, Olga Gurevitch, Sofia Khitrin, Igor B. Resnick
Department of Bone Marrow Transplantation, Hadassah Hebrew University Medical Center, P.O.B. 12000, Jerusalem 91120,
Israel; The International Center for Cell Therapy and Cancer, Tel Aviv Sourasky Medical Center, 14 Weizman Street, Tel Aviv
64239, Israel
Received June 5, 2011; accepted July 27, 2011; Epub August 22, 2011; published September 30, 2011
Abstract: Background. Donor Lymphocyte Infusion (DLI) is a well-recognized tool for augmentation of the anti-leukemia effect
after mismatched bone marrow transplantation. Experimental results show, however, that DLI efficacy is strongly dependent
on the number of donor hematopoietic cells persisting in recipient after transplantation. It is strong in mixed chimeras and
relatively weak in full chimeras (FC) that replace host antigen-presenting cells by donor antigen-presenting cells. In this study
we applied a new in vivo cytotoxicity monitoring method for evaluation of the changes in FC anti-host immunity after co-
transplantation of donor and host hematopoietic cells together. Method. Full hematopoietic chimeras and naïve control mice
were transplanted with a mixture of equivalent numbers of donor and recipient or donor and third party splenocytes labeled by
a cell-permeable fluorescent dye CFDA-SE. The animals were sacrificed at various time points, and their splenocyte
suspensions were prepared, depleted of red blood cells, stained with allophycocyanin-labeled anti-H2b antibodies, and
analyzed using fluorescence-activated cell sorting. The immune response was assessed according to the percentage of
single positive CFDA-SE+/ H2b- cells of all CFDA-SE+ cells. Results. FC grafted with splenocytes from similar FC mixed with
splenocytes from naïve host-type or third-party-type mice rejected host cells within 14 days, and third-party cells within 7 days.
NK cell depletion in vivo had no influence on host cell rejection kinetics. Co-infusion of host–type splenocytes with splenocytes
obtained from naïve donor-type mice resulted in significant acceleration of host cell rejection (10 days). Naïve mice rejected
the same amount of allogeneic lymphocytes within 3 days. Conclusions. Proposed method provides a simple and sensitive
tool to evaluate in vivo post-transplant cytotoxicity in different experimental settings. The method demonstrates that FC are
specifically deficient in their ability to reject host lymphocytes even when antigen-presenting host cells are provided. DLI
improve anti-host immune response in FC but can not restore it to the level observed in naïve donor-type mice.
(AJBR1106001).
Keywords: Transplantation, chimerism, immune response, leukemia, donor lymphocyte infusion
Full Text PDF
Address all correspondence to:
Igor B. Resnick, MD
Department of Bone Marrow Transplantation
Hadassah Hebrew University Medical Center, P.O.B. 12000,
91120, Jerusalem, Israel
E-mail: gashka@hadassah.org.il
Tel: 972-2-677-8353;
Fax: 972-2-642-2731
Igor B. Resnick: gashka@hadassah.org.il
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