In Vivo Requirements for the Immune Recognition of L1210 Leukemia Cells by Allogeneic T-Lymphocytes

1983 ◽  
Vol 69 (5) ◽  
pp. 403-408
Author(s):  
Guido Forni ◽  
Luisa Lanfrancone ◽  
Mirella Giovarelli
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Immune Recognition ◽  
L1210 Leukemia ◽  
Simultaneous Presence ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens

The resistance of normal BALB/c mice (H-2d) against the L1210 Ha leukemia of DBA/2 mouse (H-2d) origin is due to the T-lymphocyte-dependent reaction towards DBA/2 multiple minor histocompatibility antigens (Mhas). These Mhas are displayed by the leukemic cells, though in a poorly immunogenic manner. The simultaneous presence of mitomycin C-inactivated DBA/2 leukocytes induces a significantly stronger T-lymphocyte-dependent reaction. This efficient presentation of target Mhas is restricted to Ia+ leukocytes. Their presence significantly increases BALB/c resistance, even when they are injected 3 days after the L1210 Ha challenge.

scholarly journals Differential Effects of Tea Extracts on Growth and Cytokine Production by Normal and Leukemic Human Leukocytes

2012 ◽  
Vol 2 (4) ◽  
pp. 72 ◽  
Author(s):  
Diana Bayer ◽  
Jonathon Jansen ◽  
Lisa A. Beltz
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Peripheral Blood Mononuclear ◽  
Normal Cells

Background: Tea is one of the world’s most highly consumed beverages, second only to water. It is affordable and abundant and thus has great potential for improving health of those in both developed and developing areas. Green, oolong, and black teas differ in the extent of fermentation and types of bioactive polyphenols produced. Green tea and its major polyphenol decrease growth of some cancer cells and effect production of immune system cytokines. This study compares the effects of different types of tea extracts on viability and cytokine production by normal and leukemic human T lymphocytes. Generation of the toxic reactive oxygen species H2O2 by extracts was also examined.Methods: The Jurkat T lymphoblastic leukemia cells and mitogen-stimulated normal human peripheral blood mononuclear cells were used in this study. Cell viability was determined by (3-4,5-dimethylthiamizol-2-yl)-diphenyltetrazolium bromide) assay and production of interleukin-2 by Enzyme-Linked ImmunoSorbent Assay. Levels of H2O2 generated by tea extracts were determined using the xylenol-orange method.Results: We found that green, oolong, and black tea extracts differentially effect the growth and viability of T lymphoblastic leukemia cells and normal peripheral blood mononuclear cells, substantially decreasing both growth and viability of leukemic T lymphocytes and having much lesser effects on their normal counterparts. Tea extracts also had differential effects on the production of the T lymphocyte growth factor interleukin-2, significantly decreasing production by leukemic cells while having only minor effects on normal cells. All three extracts induced H2O2 generation, with green and oolong tea extracts having the greatest effect. Leukemic cells were much more susceptible to growth inhibition and killing by H2O2 than normal lymphocytes. Conclusions: The three tea extracts studied altered leukemic T lymphocyte functions, decreasing cell viability, growth, and production of a major cell growth factor and the H2O2 generated by solutions of extracts may be partially responsible. Normal cells were affected to a far lesser degree by tea extracts and are also more resistant to killing by H2O2 than leukemic cells. This study has implications for using tea extracts for chemotherapeutic and immunomodulatory purposes.Key Words: Tea extracts, interleukin-2, hydrogen peroxide, leukemia, T lymphocytes

scholarly journals Graft-host tolerance in bone marrow transplant chimeras. Absence of graft-versus-host disease is associated with unresponsiveness to minor histocompatibility antigens expressed by all tissues

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3221-3228
Author(s):  
S Brochu ◽  
C Baron ◽  
R Belanger ◽  
C Perreault
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Lymphocytes ◽  
Marrow Transplant ◽  
Lymphoid Cells ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens ◽  
Cd8 Cells ◽  
B10 Cells

Because bone marrow (BM) transplantation is used with increasing frequency, it is important to elucidate the mechanisms involved in the establishment of tolerance to host minor histocompatibility antigens (MiHA) in recipients transplanted with T-cell-undepleted marrow grafts. We have previously shown that BM chimeras transplanted across MiHA barriers showed specific unresponsiveness to MiHA expressed on recipient-type concanavalin A blasts. Because expression of many MiHA is tissue-specific, we wanted to determine if chimera T lymphocytes would be tolerant to MiHA expressed by all host tissues and organs. To investigate this issue, we measured in vivo proliferation of lymphoid cells from normal C57BL/10 (B10) mice and (B10-->LP) chimeras in tissues and organs of lethally irradiated syngeneic and allogeneic recipients. Donor B10 cells were either untreated, or depleted with anti-Thy-1.2, anti-CD4, or anti-CD8 antibodies. Transplantation of B10 cells in LP recipients triggered an important T-cell-dependent 125I- dUrd uptake in several organs that involved both CD4+ and CD8+ cells. Using Thy-1-congeneic mice we showed that in long-term chimeras practically all CD4+ and CD8+ T lymphocytes were derived from hematopoietic progenitors and not from mature T cells present in the BM graft. When (B10-->LP) BM chimera cells were injected to secondary recipients, no proliferation was observed in any organ of LP hosts whereas normal proliferation was seen in H-2k allogeneic hosts. Thus, in these BM chimeras, tolerance encompasses MiHA expressed by all organs.

Graft-host tolerance in bone marrow transplant chimeras. Absence of graft-versus-host disease is associated with unresponsiveness to minor histocompatibility antigens expressed by all tissues

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3221-3228 ◽  
Author(s):  
S Brochu ◽  
C Baron ◽  
R Belanger ◽  
C Perreault
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Lymphocytes ◽  
Marrow Transplant ◽  
Lymphoid Cells ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens ◽  
Cd8 Cells ◽  
B10 Cells

Abstract Because bone marrow (BM) transplantation is used with increasing frequency, it is important to elucidate the mechanisms involved in the establishment of tolerance to host minor histocompatibility antigens (MiHA) in recipients transplanted with T-cell-undepleted marrow grafts. We have previously shown that BM chimeras transplanted across MiHA barriers showed specific unresponsiveness to MiHA expressed on recipient-type concanavalin A blasts. Because expression of many MiHA is tissue-specific, we wanted to determine if chimera T lymphocytes would be tolerant to MiHA expressed by all host tissues and organs. To investigate this issue, we measured in vivo proliferation of lymphoid cells from normal C57BL/10 (B10) mice and (B10-->LP) chimeras in tissues and organs of lethally irradiated syngeneic and allogeneic recipients. Donor B10 cells were either untreated, or depleted with anti-Thy-1.2, anti-CD4, or anti-CD8 antibodies. Transplantation of B10 cells in LP recipients triggered an important T-cell-dependent 125I- dUrd uptake in several organs that involved both CD4+ and CD8+ cells. Using Thy-1-congeneic mice we showed that in long-term chimeras practically all CD4+ and CD8+ T lymphocytes were derived from hematopoietic progenitors and not from mature T cells present in the BM graft. When (B10-->LP) BM chimera cells were injected to secondary recipients, no proliferation was observed in any organ of LP hosts whereas normal proliferation was seen in H-2k allogeneic hosts. Thus, in these BM chimeras, tolerance encompasses MiHA expressed by all organs.

H-2-restriction and Ia-dependence of the efficient immune recognition of minor histocompatibility antigens in vivo

1979 ◽  
Vol 9 (1) ◽  
pp. 199-202 ◽  
Author(s):  
Guido Forni ◽  
Mirella Giovarelli ◽  
Alessandro Negro-Ponzi ◽  
Santo Landolfo
Keyword(s):  
Immune Recognition ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens

Feasibility of Immunotherapy of Relapsed Leukemia With Ex Vivo–Generated Cytotoxic T Lymphocytes Specific for Hematopoietic System-Restricted Minor Histocompatibility Antigens

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2336-2341 ◽  
Author(s):  
Tuna Mutis ◽  
Rob Verdijk ◽  
Ellen Schrama ◽  
Bennie Esendam ◽  
Anneke Brand ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Ex Vivo ◽  
Allogeneic Bone Marrow Transplantation ◽  
Leukemic Cells ◽  
Allogeneic Bone ◽  
Histocompatibility Antigens ◽  
Lymphoid Leukemia ◽  
Minor Histocompatibility Antigens ◽  
Specific Ctls

Abstract Allogeneic bone marrow transplantation (BMT) is a common treatment of hematologic malignancies. Recurrence of the underlying malignancy is a major cause of treatment failure. Donor-derived cytotoxic T lymphocytes (CTLs) specific for patients’ minor histocompatibility antigens (mHags) play an important role in both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) reactivities. mHags HA-1 and HA-2 induce HLA-A*0201-restricted CTLs in vivo and are exclusively expressed on hematopoietic cells, including leukemic cells and leukemic precursors, but not on fibroblasts, keratinocytes, or liver cells. The chemical nature of the mHags HA-1 and HA-2 is known. We investigated the feasibility of ex vivo generation of mHag HA-1– and HA-2–specific CTLs from unprimed mHag HA-1– and/or HA-2–negative healthy blood donors. HA-1 and HA-2 synthetic peptide-pulsed dendritic cells (DCs) were used as antigen-presenting cells (APC) to stimulate autologous unprimed CD8+ T cells. The ex vivo–generated HA-1– and HA-2–specific CTLs efficiently lyse leukemic cells derived from acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) patients. No lytic reactivity was detected against nonhematopoietic cells. Sufficient numbers of the CTLs can be obtained for the adoptive immunotherapy purposes. In conclusion, we present a feasible, novel therapy for the treatment for relapsed leukemia after BMT with a low risk of GVHD.

Feasibility of Immunotherapy of Relapsed Leukemia With Ex Vivo–Generated Cytotoxic T Lymphocytes Specific for Hematopoietic System-Restricted Minor Histocompatibility Antigens

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2336-2341 ◽  
Author(s):  
Tuna Mutis ◽  
Rob Verdijk ◽  
Ellen Schrama ◽  
Bennie Esendam ◽  
Anneke Brand ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Ex Vivo ◽  
Allogeneic Bone Marrow Transplantation ◽  
Leukemic Cells ◽  
Allogeneic Bone ◽  
Histocompatibility Antigens ◽  
Lymphoid Leukemia ◽  
Minor Histocompatibility Antigens ◽  
Specific Ctls

Allogeneic bone marrow transplantation (BMT) is a common treatment of hematologic malignancies. Recurrence of the underlying malignancy is a major cause of treatment failure. Donor-derived cytotoxic T lymphocytes (CTLs) specific for patients’ minor histocompatibility antigens (mHags) play an important role in both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) reactivities. mHags HA-1 and HA-2 induce HLA-A*0201-restricted CTLs in vivo and are exclusively expressed on hematopoietic cells, including leukemic cells and leukemic precursors, but not on fibroblasts, keratinocytes, or liver cells. The chemical nature of the mHags HA-1 and HA-2 is known. We investigated the feasibility of ex vivo generation of mHag HA-1– and HA-2–specific CTLs from unprimed mHag HA-1– and/or HA-2–negative healthy blood donors. HA-1 and HA-2 synthetic peptide-pulsed dendritic cells (DCs) were used as antigen-presenting cells (APC) to stimulate autologous unprimed CD8+ T cells. The ex vivo–generated HA-1– and HA-2–specific CTLs efficiently lyse leukemic cells derived from acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) patients. No lytic reactivity was detected against nonhematopoietic cells. Sufficient numbers of the CTLs can be obtained for the adoptive immunotherapy purposes. In conclusion, we present a feasible, novel therapy for the treatment for relapsed leukemia after BMT with a low risk of GVHD.

scholarly journals O10: METFORMIN TREATMENT IMPROVES LYMPHOCYTE METABOLISM IN A MOUSE MODEL OF MAJOR SURGERY

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
TF Jones ◽  
A Gutierrez ◽  
del Arroyo ◽  
SM Henson ◽  
GL Ackland
Keyword(s):  
T Lymphocytes ◽  
Mouse Model ◽  
T Lymphocyte ◽  
Major Surgery ◽  
P Value ◽  
Free Access ◽  
Mitochondrial Bioenergetics ◽  
Metformin Treatment ◽  
Respiratory Capacity

Abstract Introduction Lymphopaenia is common after major surgery and associated with poor outcome. T-lymphocytes restrain damaging innate inflammation. Major surgery impairs T-lymphocyte metabolism in humans, which promotes lymphopaenia. Metformin is known to improve mitochondrial bioenergetics in models of inflammation. Firstly, we hypothesised that a mouse model of major surgery would demonstrate impaired T-lymphocyte metabolism and secondly, that metformin treatment in vivo would reverse the phenotype. Method Male C57Bl/6 mice aged between 8 and 12 weeks were housed in a specific pathogen free environment with free access to food and water. Animals were dosed with either vehicle (phosphate buffered saline, 20 ml/kg) or metformin (250 mg/kg) daily via intraperitoneal injection for four days prior to and after surgery. A partial hepatectomy was performed under isofluorane anaesthesia. Naive littermates were used as controls. All experiments were performed according to the Animals (Scientific Procedures) Act 1986. Splenic T-lymphocytes were isolated by negative selection using magnetic beads. Mitochondrial bioenergetics were measured using a Seahorse Extracellular Flux analyser. Parametric statistical analysis was performed and a p-value < 0.05 was chosen to represent significance. Result T-lymphocytes demonstrated reduced spare respiratory capacity (SRC, 285 vs 497 %, p=0.004) after surgery compared to naive controls. Metformin treatment in vivo reversed this observation and SRC was comparable to naive (437 vs 497 %, p=0.34). Metformin treatment in vitro increased spare respiratory capacity in T-lymphocytes from mice after surgery compared to naive (change from untreated, 187 vs 91 %, p=0.03). Conclusion Perioperative metformin treatment improved T-lymphocyte metabolism in a mouse model of major surgery. Take-home message Metformin is a potential treatment for the lymphocyte metabolic dysfunction observed after surgery.

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