Costimulatory signals through interaction of B7.1 and CD28 prevent “veto” death of cytotoxic T cells during tumor target cell lysis

Daniel, Pascale; Kroidl, Arne; Bargou, Ralf C.; Cayeux, S; Blankenstein, T; Pezzutto, Antonio; Dörken, Bernd

doi:10.1016/s0959-8049(97)89423-3

Cited by 32 publications

(50 citation statements)

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“…There have been reports of CD28 having both pro-apoptotic 46,47 and anti-apoptotic effects. [48][49][50] Studies on the aging immune system have found that the number of CD8 þ CD28 À T cells increases with age and that these cells are resistant to apoptosis, having increased bcl-2 expression and decreased caspase 3 expression. [51][52][53] In addition, CD8 þ CD28 À T cells have been reported to have regulatory functions; CD8 þ CD28 À T cells have been implicated in tolerance in studies of cardiac transplant recipients, 54 in decreased antibody production following immunization in elderly patients 55 and tumor susceptibility and growth in cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Distinct gene signature revealed in white blood cells, CD4+ and CD8+ T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide

et al. 2010

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Tolerizing mice polygenically predisposed to lupus-like disease (NZB/NZW F1 females) with a peptide mimicking anti-DNA IgG sequences containing MHC class I and class II T cell determinants (pConsensus, pCons) results in protection from full-blown disease attributable in part to the induction of CD4 þ CD25 þ Foxp3 þ and CD8 þ Foxp3 þ regulatory T cells. We compared 45 000 murine genes in total white blood cells (WBC), CD4 þ T cells, and CD8 þ T cells from splenocytes of (NZBxNZW) F1 lupus-prone mice tolerized with pCons vs untreated naïve mice and found two-fold or greater differential expression for 448 WBC, 174 CD4, and 60 CD8 genes. We identified differentially expressed genes that played roles in the immune response and apoptosis. Using real-time PCR, we validated differential expression of selected genes (IFI202B, Bcl2, Foxp3, Trp-53, CCR7 and IFNar1) in the CD8 þ T cell microarray and determined expression of selected highly upregulated genes in different immune cell subsets. We also determined Smads expression in different immune cell subsets, including CD4 þ T cells and CD8 þ T cells, to detect the effects of TGF-b, known to be the major cytokine that accounts for the suppressive capacity of CD8 þ Treg in this system. Silencing of anti-apoptotic gene Bcl2 or interferon genes (IFI202b and IFNar1 in combination) in CD8 þ T cells from tolerized mice did not affect the expression of the other selected genes. However, silencing of Foxp3 reduced expression of Foxp3, Ifi202b and PD1-all of which are involved in the suppressive capacity of CD8 þ Treg in this model.

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Section: Discussionmentioning

confidence: 99%

Distinct gene signature revealed in white blood cells, CD4+ and CD8+ T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide

et al. 2010

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“…This finding may be because costimulation via CD28 decreases the probability for lymphocytes to undergo apoptosis (27,28), providing them with a long lifespan in vitro (19). Costimulated lymphocytes also have survived for a long time after transfer back to autologous patients (29) as opposed to lymphocytes expanded in the presence of high doses of IL-2.…”

Section: Discussionmentioning

confidence: 99%

CD3-mediated activation of tumor-reactive lymphocytes from patients with advanced cancer

Hellström¹,

Ledbetter²,

Scholler³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Lymphocytes from blood or tumors of patients with advanced cancer did not proliferate and produced very low levels of tumor necrosis factor and IFN-␥ when cultured with autologous tumor cells. Proliferation and lymphokine production dramatically increased in the presence of beads conjugated with mAbs to CD3 plus mAbs to CD28 and͞or CD40, and the lymphocytes destroyed the tumor cells. Expression density of CD3 concomitantly increased from low to normal levels. Furthermore, beads providing a CD3 signal (in combination with CD28 or CD28 plus CD40) gave partial protection against the inhibitory effect of transforming growth factor type ␤1 on lymphocyte proliferation and production of tumor necrosis factor and IFN-␥. MHC class I-restricted cytolytic T cells lysing autologous tumor cells in a 4-h Cr 51 release assay were generated when peripheral blood leukocytes were activated in the presence of autologous tumor cells and anti-CD3͞CD28 or anti-CD3͞CD28͞CD40 beads. Experiments performed in a model system using anti-V-␤1 or anti-V-␤2 mAbs to activate subsets of T cells expressing restricted T cell receptor showed that lymphocytes previously activated by anti-V-␤ can respond to CD3 stimulation with vigorous proliferation and lymphokine production while retaining their specificity, also in the presence of transforming growth factor type ␤1. Our results suggest that T lymphocytes from cancer patients can proliferate and form Th1 type lymphokines in the presence of autologous tumor cell when properly activated, and that antigen released from killed tumor cells and presented by antigenpresenting cells in the cultures facilitates the selective expansion of tumor-directed, CD8 ؉ cytolytic T cells.immunotherapy ͉ tumor vaccines ͉ tumor immunity ͉ transforming growth factor type ␤1

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“…In line with this, tumor cell transfection with B7.1/CD80 has been shown to facilitate T-cell effector functions, e.g., proliferation and tumor cell lysis, and to inhibit activation induced T-cell death. 22 Irradiation of such tumor cell vaccines prior to transfer into patients is a prerequisite in many human preclinical and clinical trials. Previous data indicated that ionizing irradiation impairs the generation of tumor immunity in vivo.…”

Section: Tumor Cell Irradiation Does Not Influence Transgene Expressionmentioning

confidence: 99%

Necrotic death but not irradiation abolishes costimulation of T‐cell effector functions and survival by CD80‐expressing tumor cells

Stärck

Schölz

Blankenstein

et al. 2005

Intl Journal of Cancer

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Tumor vaccination by the use of gene‐modified cancer cells that provide costimulatory signals has been successfully applied in preclinical animal models and is currently evaluated in a variety of clinical settings. In previous work, we demonstrated the efficacy of B7.1/CD80 to promote tumor immunity in syngeneic murine models and to prevent deletion of activated T cells by activation‐induced cell death (AICD). In clinical trials, tumor cell vaccines are generally inactivated to avoid transfer of live tumor cells, i.e., additional tumor burden. Previous data indicated, however, that inactivation of tumor cells by lethal ionizing irradiation abrogates tumor vaccination by CD80‐expressing cells. Here, we compare living and irradiated allogeneic tumor cells regarding their capacity to induce T‐cell effector functions and their propensity to interfere with T‐cell deletion by apoptosis. Both lethally irradiated and nonirradiated tumor cells facilitated T‐cell proliferation, tumor cell lysis, and interfered with T‐cell AICD to a similar extent. In contrast, necrotic tumor cells failed to costimulate T‐cell effector functions. Thus, irradiation does not seem to hamper tumor cell‐mediated costimulation of T‐cell effector functions. In contrast, necrosis of gene‐modified tumor cells abrogates costimulation of T cells by CD80‐expressing cells. © 2005 Wiley‐Liss, Inc.

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Costimulatory signals through interaction of B7.1 and CD28 prevent “veto” death of cytotoxic T cells during tumor target cell lysis

Cited by 32 publications

References 0 publications

Distinct gene signature revealed in white blood cells, CD4+ and CD8+ T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide

Distinct gene signature revealed in white blood cells, CD4+ and CD8+ T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide

CD3-mediated activation of tumor-reactive lymphocytes from patients with advanced cancer

Necrotic death but not irradiation abolishes costimulation of T‐cell effector functions and survival by CD80‐expressing tumor cells

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