Ontogenic and functional implications of the differential expression of HLA-DQ antigens on leukemic cells

Navarrete, C.; Fernández, Nelson; Alonso, M. C.; Festenstein, H.

doi:10.1016/0198-8859(86)90035-2

Cited by 16 publications

(6 citation statements)

References 29 publications

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“…HLA class II restricted TCRs directed against hematopoiesis-specific antigens which are differentially expressed between the patient and donor can be very suitable for the treatment of hematological malignancies, 42 since HLA class II expression is not only found on hematopoietic progenitor cells, 43 B cells, 44 activated T cells, 44 and monocytes, 44 but also on many malignant hematopoietic cells. HLA class II expression has been demonstrated on acute myeloid leukemia, 45,46 chronic myeloid leukemia, 47 acute lymphoblastic leukemia, 46,48,49 chronic lymphocytic leukemia, 46,49 multiple myeloma, 50 and hairy cell leukemia. 48 Thus, HLA class II restricted TCR-transferred CD4 + T cells combining cytolytic activity with cytokine production may therefore be very potent effector cells for the application of cellular immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

HLA class II restricted T-cell receptor gene transfer generates CD4+ T cells with helper activity as well as cytotoxic capacity

et al. 2005

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Both cytotoxic T cells and helper T cells are important in immune responses against pathogens and malignant cells.In hematological malignancies which express HLA class II molecules, immunotherapy may be directed to HLA class II restricted antigens. We investigated whether it is possible to engineer HLA class II restricted T cells with both antigenspecific cytolytic activity and the capacity to produce high amounts of cytokines. CD4 + and CD8 + peripheral-bloodderived T cells were retrovirally transduced with the HLA class II restricted minor histocompatibility antigen dead box RNA helicase Y (DBY)-specific TCR. The TCR-transduced CD4 + T cells exerted DBY-specific cytolytic activity, produced Th0, Th1, or Th2 cytokines, and proliferated upon DBY-specific stimulation. TCR-transduced CD8 + T cells exerted cytolytic activity which equaled the level of cytolytic activity of the TCR-transferred CD4 + T cells. Cotransfer of CD4 enhanced the cytolytic activity of the TCR-transduced CD8 + T cells, but introduction of CD4 was not sufficient to generate DBY-specific CD8 + T cells with the capacity to produce high amounts of cytokines. In this study, we demonstrated the feasibility to engineer T cells with antigen-specific cytolytic activity, as well as the ability to produce significant amounts of cytokines, by TCR transfer to CD4 + T cells. Gene Therapy (2005) IntroductionPatients relapsing from leukemia after allogeneic stem cell transplantation can successfully be treated by donor lymphocyte infusions (DLI), due to the graft-versusleukemia (GVL) response of the donor-derived T cells. [1][2][3][4] However, DLI is also associated with graft-versus-hostdisease (GVHD). Several studies have illustrated that depletion of CD8 + T cells from the DLI may preserve the beneficial GVL reactivity without the induction of GVHD, indicating that the CD4 + T lymphocytes may play an essential role in the antileukemic reactivity. [5][6][7][8][9][10] The mechanism by which the CD4 + T cells contribute to the GVL response is, however, not known. CD4 + T cells have been suggested to elicit the antileukemic response via the induction of minor histocompatibility antigen (mHag)-specific CD8 + T cells. 5 In addition, mHag-specific CD4 + T-helper cells have been reported to mature dendritic cells and enhance the expansion of mHag-specific cytotoxic T lymphocytes in vitro. 11 Alternatively, we have demonstrated that CD4 + T cells are capable of exerting direct cytolytic activity against leukemic cells. [12][13][14] Cellular immunotherapeutic approaches based on the adoptive transfer of T lymphocytes may require large cell numbers. Large numbers of T cells with a defined antigen specificity can be acquired by retroviral transfer of the T-cell receptor to peripheral-blood-derived T lymphocytes. Until now, the application of retroviral transfer of TCRs has mainly been limited to the transfer of HLA class I restricted TCRs. [15][16][17][18][19][20] However, the specificity of HLA class II restricted T lymphocytes can also be transferred to other T c...

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Section: Discussionmentioning

confidence: 99%

HLA class II restricted T-cell receptor gene transfer generates CD4+ T cells with helper activity as well as cytotoxic capacity

et al. 2005

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“…We have previously shown that HLA-DR and HLA-DQ molecules differ in their expression on normal and leukaemic cells of myelomonocytic origin (Navarrete et al, 1981(Navarrete et al, , 1984(Navarrete et al, , 1985Alonso et al, 1985a,b). Whereas acute myeloblastic leukaemia (AML) blasts express HLA-DR antigens, HLA-DQ molecules are absent from these cells.…”

Section: Introductionmentioning

confidence: 99%

Modulation of the Expression of Hla Class Ii Antigens by Gamma Interferon and Phorbol Ester Tpa on Myeloid Leukaemic Cell Lines

Alonso

Navarrete

Solana

et al. 1986

Int J Immunogenetics

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SUMMARY We investigated the effect of gamma interferon and phorbol ester (TPA), on the expression of HLA class II molecules of myeloid leukaemic cell lines K562, U937, KG‐1, HG60 and ML‐2. Gamma interferon induced the expression of HLA‐DR but not HLA‐DQ on HL‐60 and ML‐2, increased the expression of HLA‐DR and DQ on U937 and induced the expression of HLA‐DQ on KG‐1. TPA treatment did not affect the expression of HLA class II antigens on U937 and KG‐I and induced the expression of HLA‐DR and HLA‐DQ on HL‐60 and ML‐2. TPA treatment did not affect the HLA phenotype of K562 but gamma interferon did induce HLA class I molecules. Thus, gamma interferon cannot only increase the expression of HLA products already expressed on the cells but can also induce the de novo synthesis of these molecules on myeloid leukaemic cell lines.

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“…On the other hand, it has been demonstrated that certain undifferentiated human solid tumors [5,14], leukemias [2,3,15] and normal hemopoietic cells [1] express a low level of HLA. In such cases the reduced levels of MHC antigens can enable tumor cells to avoid lysis by specific cytotoxic T cells and the role of NK cells in tumor immune surveillance would be of particular relevance.…”

Section: Discussionmentioning

confidence: 99%

Natural Killer Susceptibility of Brain Tumor Cell Lines Inversely Correlates with the Degree of Cell Differentiation and Not with the Level of Human Histocompatibility Antigen Expression

Alonso

Serrano²,

Solana³

et al. 1989

Int Arch Allergy Immunol

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The purpose of this paper is to investigate the natural killer (NK) sensitivity of 15 cell lines derived from human brain tumors expressing different levels of major histocompatibility complex (MHC) antigens. Although it has recently been reported that NK susceptibility varies inversely with target cell class-I human leukocyte antigen (HLA) expression, our results show no correlation between class-I HLA, class-II HLA or β₂-microglobulin expression on target cells and NK sensitivity, whereas a significant inverse correlation between NK susceptibility and the degree of tumor cell differentiation has been found. Thus, poorly differentiated tumor cells are highly susceptible to NK lysis, whereas well-differentiated ones are NK resistant. These results suggest that sensitivity to lysis by NK cells of cell lines derived from human brain tumors is primarily determined by the stage of differentiation and not by the level of MHC antigen expression on target cell.

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Ontogenic and functional implications of the differential expression of HLA-DQ antigens on leukemic cells

Cited by 16 publications

References 29 publications

HLA class II restricted T-cell receptor gene transfer generates CD4+ T cells with helper activity as well as cytotoxic capacity

HLA class II restricted T-cell receptor gene transfer generates CD4+ T cells with helper activity as well as cytotoxic capacity

Modulation of the Expression of Hla Class Ii Antigens by Gamma Interferon and Phorbol Ester Tpa on Myeloid Leukaemic Cell Lines

Natural Killer Susceptibility of Brain Tumor Cell Lines Inversely Correlates with the Degree of Cell Differentiation and Not with the Level of Human Histocompatibility Antigen Expression

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