The Molecular Basis for Cytolytic T Lymphocyte Function: Analysis with Blocking Monoclonal Antibodies

Martz, Eric; Davignon, Denise; Kürzinger, Konrad; Springer, Timothy A.

doi:10.1007/978-1-4684-8959-0_27

Cited by 17 publications

(10 citation statements)

References 76 publications

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“…LFA-1/ICAM-1 interaction is known from in vitro studies to provide costimulation signals to CD8 + T cells (independent of CD28/B7) (31,(35)(36)(37), and to provide adhesion necessary for cytotoxic T-cell (CTL) effector function (26,28). We have previously noted that hepatocytes constitutively express ICAM-1 which is up-regulated by the inflammatory cytokine TNF-a.…”

Section: Discussionmentioning

confidence: 99%

“…It is also expressed on a large fraction of bone marrow cells (26) and leukocytes (27). The role of LFA-1 as an adhesion molecule which participates in cytotoxic T-cell (CTL) target interaction is well known (26,28). LFA-1 also functions as a costimulation molecule that provides the second signal upon the T-cell receptor (TCR) engagement (29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

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Targeting LFA-1 Synergizes with CD40/CD40L Blockade for Suppression of Both CD4-Dependent and CD8-Dependent Rejection

Wang

Gao

Lunsford

et al. 2003

American Journal of Transplantation

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Allogeneic hepatocytes elicit CD4-dependent and (CD4-independent) CD8 + T-cell-initiated graft rejection. The (CD4-independent) CD8 + T-cell pathway is resistant to immunosuppressive strategies that readily and indefinitely suppress CD4 + T-cell-dependent rejection responses. Consequently, successful immunoregulation of hepatocyte-initiated immune responses requires a strategy which regulates both CD4-dependent and CD8-dependent rejection responses. Interference with CD40/CD40 ligand (CD40L) costimulation only transiently suppresses CD4-and CD8-dependent hepatocyte rejection. Interference with CD28/B7 costimulation transiently suppresses CD4-dependent hepatocyte rejection, but is ineffective for suppression of CD8-dependent hepatocyte rejection. To date, hepatocyte survival > 60 days post-transplant has not been achieved by any immunotherapeutic strategy. In the current study, we evaluated a novel immunosuppressive strategy which targets both LFA-1 and CD40L-mediated signals. Targeting LFA-1 suppressed (CD4-independent) CD8 + T-cell-initiated hepatocyte rejection such that allogeneic hepatocyte survival > 60 days was achieved in 70% of CD4 KO mice. Targeting both LFA-1-mediated signals and CD40/CD40L costimulation resulted in synergistic effects, such that hepatocellular survival > 60 days was achieved in 100% of C57BL/6 mice (which have both CD4-and CD8-dependent T-cell pathways available).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting LFA-1 Synergizes with CD40/CD40L Blockade for Suppression of Both CD4-Dependent and CD8-Dependent Rejection

Wang

Gao

Lunsford

et al. 2003

American Journal of Transplantation

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“…During the I970's, there were many attempts to block CTL function with antisera (reviewed in Martz et al 1982a). Blocking was obtained with antisera to the specific target-cell antigens recognized by the CTL, but blocking with antisera directed against CTL structures was difficult to achieve.…”

Section: Identification Of Ctl Blocking Sites With Monoclonal Antibodiesmentioning

confidence: 99%

“…Cytolytic thytnus-derived lymphocytes (CTL)' are believed to play a crucial role in immunity to virus infections (Lin & Askonas 1981), some types of tumors (Brunner et al 1981, Cheever et al 1982, and in some forms of allograft rejection (Engers et al 1982). Since the recognition of CTL as a distinct effector cell 15-20 years ago, considerable research has been devoted to understanding the lytic mechanism employed by these cells (reviewed in Martz 1977, Berke 1980, Sanderson 1981, Martz et al 1982a, Martz et al 1982b.…”

Section: Introductionmentioning

confidence: 99%

The Mechanism of CTL‐Mediated Killing: Monoclonal Antibody Analysis of the Roles of Killer and Target‐Cell Membrane Proteins

Martz

Heagy

Gromkowski

1983

Immunological Reviews

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“…growth properties and susceptibility to cytotoxicity, the latter being correlated with the level of some molecules on the tumor cell surface, such as MHC class I or II molecules, ICAM-1, LFA-3 etc. (Martz et al 1982;Anichini et al 1990). …”

Section: Discussionmentioning

confidence: 96%

Involvement of MHC class I molecule and ICAM-1 in the enhancement of adhesion and cytotoxic susceptibility to immune effector cells of tumor cells transfected with the interleukin (IL)-2, IL-4 or IL-6 gene

Cao

Chen

et al. 1997

Journal of Cancer Research and Clinical Oncology

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To investigate the molecular and cellular mechanisms involved in the reduced tumorigenicity and increased immunogenicity of interleukin-2 (IL-2)-, IL-4- or IL-6-gene-transfected B16 melanoma vaccine, we have analyzed the functional and phenotypic properties of these genetically engineered melanoma cells in the present study. The cytokine-gene-transfected B16 melanoma cells showed stronger adhesion to the lymphokine-activated killer (LAK) cells or cytotoxic T lymphocytes (CTL), and higher sensitivity to cytotoxicity of LAK cells or CTL. Using fluorescence-activated cell sorting analysis, we found that both MHC class I and ICAM-1 expression were increased after IL-2, IL-4 or IL-6 gene transfection. The increased level of MHC class I and ICAM-1 expression seems to be responsible for the high sensitivity of these gene-transfected B16 cells to LAK or CTL cytotoxicity because anti-(MHC class I) or anti-ICAM-1 mAb could inhibit the adhesion and cytotoxicity increment simultaneously. The CTL induction was partly inhibited by anti-ICAM-1 mAb and was completely blocked by anti-MHC class I mAb. These results suggested that the decreased tumorigenicity of IL-2-, IL- 4-, and IL-6-gene-transfected B16 melanoma cells may be partly due to the increased sensitivity to effector cell cytotoxicity mediated by increased expression of ICAM-1 or MHC class I molecules on the tumor cell surface after cytokine gene transfection.

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The Molecular Basis for Cytolytic T Lymphocyte Function: Analysis with Blocking Monoclonal Antibodies

Cited by 17 publications

References 76 publications

Targeting LFA-1 Synergizes with CD40/CD40L Blockade for Suppression of Both CD4-Dependent and CD8-Dependent Rejection

Targeting LFA-1 Synergizes with CD40/CD40L Blockade for Suppression of Both CD4-Dependent and CD8-Dependent Rejection

The Mechanism of CTL‐Mediated Killing: Monoclonal Antibody Analysis of the Roles of Killer and Target‐Cell Membrane Proteins

Involvement of MHC class I molecule and ICAM-1 in the enhancement of adhesion and cytotoxic susceptibility to immune effector cells of tumor cells transfected with the interleukin (IL)-2, IL-4 or IL-6 gene

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