Comparison of in Vivo and in Vitro Immune Response to Purified Hepatocytes

Bumgardner, Ginny L.; Matas, Arthur J.; Chen, Sally; Cahill, D R; Cunningham, Thomas J.; Payne, William D.; Bach, Fritz H.; Ascher, Nancy L.

doi:10.1097/00007890-199002000-00039

Cited by 43 publications

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“…[12][13][14][18][19][20][21] The contribution of non-MHC molecules such as adhesion molecules ICAM-1 and VCAM-1 to immune recognition of allogeneic hepatocytes is unknown and has implications for both rejection after solid organ liver transplants and after hepatocellular transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…12 We have further demonstrated that purified hepatocytes are immunogenic in vivo and stimulate the development of allo-CTLs in sponge matrix allografts (SMA) bearing allogeneic hepatocytes. 13,14 In this report, we extend our previous in vivo studies using the hepatocytesponge matrix allograft (HC-SMA) model to examine the role of ICAM-1 and VCAM-1 adhesion molecules on in vivo host immune responses to allogeneic hepatocytes.The SMA model has been adapted and used extensively to study in vivo host immune responses to various allogeneic cells. In this model, a sponge matrix is ''grafted'' with cells isolated from a different mouse strain (MHC-mismatched allogeneic ''donor'' cells), and the SMA is then implanted subcutaneously onto a ''host'' mouse.…”

mentioning

confidence: 89%

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confidence: 89%

“…Such studies have previously been pursued using the HC-SMA and have revealed that the peak development of allo-CTLs in response to allogeneic hepatocytes occurs on day 12 to 14 after grafting. 13 In addition, these prior studies have revealed the importance of expression of MHC class I on the ''donor'' hepatocyte population in the stimulation of the observed cytolytic response, that this response is reproducible in a number of MHC-mismatched host/donor strain combinations, and that the cytotoxic effector cell in HC-SMA is a CD8 ϩ , CD4 Ϫ T cell. 13 In the current studies, the HC-SMA model is employed to determine the role of expression of ICAM-1 and/or VCAM-1 on ''donor'' hepatocytes on the subsequent attraction of host cells to the sponge allograft and on the development of allo-CTLs in HC-SMA.…”

mentioning

confidence: 99%

“…13 In addition, these prior studies have revealed the importance of expression of MHC class I on the ''donor'' hepatocyte population in the stimulation of the observed cytolytic response, that this response is reproducible in a number of MHC-mismatched host/donor strain combinations, and that the cytotoxic effector cell in HC-SMA is a CD8 ϩ , CD4 Ϫ T cell. 13 In the current studies, the HC-SMA model is employed to determine the role of expression of ICAM-1 and/or VCAM-1 on ''donor'' hepatocytes on the subsequent attraction of host cells to the sponge allograft and on the development of allo-CTLs in HC-SMA. The expression of adhesion molecules ICAM-1 and VCAM-1 on parenchymal and liver nonparenchymal cells is described, and the effect of monoclonal antibodies (mAb) directed against ICAM-1 and VCAM-1 on in vivo cellular immune responses to allogeneic parenchymal liver cells (hepatocytes) is investigated.…”

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confidence: 99%

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Efficacy of anti-intercellular adhesion molecule-1 immunotherapy on immune responses to allogeneic hepatocytes in mice

Bumgardner

Heininger

et al. 1998

Hepatology

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Adhesion molecules appear to play important roles in vascularized organ allograft rejection, because antibodies directed against them are effective in prolonging survival of vascularized organ allografts in rodents. However, the efficacy of these agents for cellular allografts is unknown. The current studies were undertaken to determine the role of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on host immune responses to purified hepatocytes. Host mice (C3H, H-2 k ) grafted with hepatocytes in sponge matrix allografts (HC-SMA) received IgG isotype control, anti-ICAM-1, or anti-VCAM-1 monoclonal antibody (mAb) on days 0 through 9 after grafting. Twelve to 14 days later, host cells infiltrating the HC-SMA were assessed for the development of allospe- Adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are expressed on endothelial and some parenchymal cells. These adhesion molecules (ICAM-1 and VCAM-1) also appear to play important roles in vascularized organ allograft rejection, because antibodies directed against ICAM-1 and VCAM-1 have been shown to be effective in prolonging survival of vascularized murine cardiac allografts, cynomolgous monkey renal transplants, and human renal transplants, [1][2][3][4][5][6] as well as nonvascularized skin allografts. 7 ICAM-1 has been implicated in liver transplant rejection by studies that show increased levels of soluble ICAM-1 during rejection episodes and histological detection of increased ICAM-1 during liver allograft rejection. [8][9][10] Parenchymal cells may constitutively express or may be induced to express adhesion molecules by various cytokines. However, the role of adhesion molecules in the presentation of major histocompatibility complex (MHC) antigens by parenchymal cells is not known. Cytokines, including interleukin-1, interferon gamma, and tumor necrosis factor (TNF), have been shown to up-regulate hepatocyte expression of ICAM-1 and their adhesion to T lymphocytes in vitro. 11 However, the in vivo effects of various cytokines on adhesion molecule expression in the liver has not been described, and the consequences of in vivo cytokine exposure upon the immunogenicity of liver cells has not been reported.Previously, we demonstrated that purified hepatocytes in the absence of donor-type antigen-presenting cells are immunogenic in vitro in mixed lymphocyte hepatocyte culture as determined by their ability to stimulate proliferation and the development of allospecific cytolytic effector T cells (alloCTLs) in mixed lymphocyte hepatocyte culture. The observed immunogenicity was correlated with the expression of MHC class I antigens. 12 We have further demonstrated that purified hepatocytes are immunogenic in vivo and stimulate the development of allo-CTLs in sponge matrix allografts (SMA) bearing allogeneic hepatocytes. 13,14 In this report, we extend our previous in vivo studies using the hepatocytesponge matrix allograft (HC-SMA) model to examine the role of ICA...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 89%

mentioning

confidence: 89%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Efficacy of anti-intercellular adhesion molecule-1 immunotherapy on immune responses to allogeneic hepatocytes in mice

Bumgardner

Heininger

et al. 1998

Hepatology

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Evaluation of a nuclear score for p16INK4a-stained cervical squamous cells in liquid-based cytology samples

Wentzensen

Bergeron²,

Frederic³

et al. 2005

Cancer

101

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The 546‐base pair enhancer of limb expression HACNS1, which is highly constrained in all terrestrial vertebrates, has accumulated 16 human‐specific changes after the human‐chimpanzee split. There has been discussion whether this process was driven by positive selection or biased gene conversion, without considering population data. We studied 83 South Amerindian, 11 Eskimo, 35 Europeans, 37 Bantu, and non‐Bantu Sub‐Saharan speakers, and 28 Brazilian mestizo samples and found no variation in this DNA region. Similar lack of variability in this region was found in four Africans, five Europeans or Euro‐derived, two Asians, one Paleo‐Eskimo, and one Neandertal sequence, whose whole genomes are publicly available. No difference was found. This result favors the interpretation of past positive and present conservative selection, as would expected in a region which influences Homo‐specific traits as important as opposable thumbs, manual dexterity, and bipedal walking. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.

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Hepatocyte transplantation: Back to the future

Gupta

Chowdhury

1992

Hepatology

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Comparison of in Vivo and in Vitro Immune Response to Purified Hepatocytes

Cited by 43 publications

References 0 publications

Efficacy of anti-intercellular adhesion molecule-1 immunotherapy on immune responses to allogeneic hepatocytes in mice

Efficacy of anti-intercellular adhesion molecule-1 immunotherapy on immune responses to allogeneic hepatocytes in mice

Evaluation of a nuclear score for p16INK4a-stained cervical squamous cells in liquid-based cytology samples

Hepatocyte transplantation: Back to the future

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