Cytotoxic activity of graft-infiltrating lymphocytes correlates with cellular rejection in cardiac transplant patients

Frisman, Dennis M.; Fallon, John T.; Hurwitz, Alfred; Dec, William G.; Kurnick, James T.

doi:10.1016/0198-8859(91)90086-o

Cited by 17 publications

(4 citation statements)

References 7 publications

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“…These in vitro results indicated that antiproliferative effects and induction of apoptosis in CD8+ and NK cells were two clearly independent mechanisms. This observation seems to be of particular interest in the setting of allo‐immmune response as cytotoxic CD8+ cells are known to be primarily responsible for acute allograft rejection [30,31].…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus hyperimmunoglobulin: mechanisms in allo‐immune response in vitro

Höetzenecker

Hacker

Hoetzenecker

et al. 2007

Eur J Clin Investigation

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Section: Discussionmentioning

confidence: 99%

Cytomegalovirus hyperimmunoglobulin: mechanisms in allo‐immune response in vitro

Höetzenecker

Hacker

Hoetzenecker

et al. 2007

Eur J Clin Investigation

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“…Although it is not known whether the initial T cell proliferation occurs within the tumor nodules or elsewhere, such as lymphoid tissues, it is clear that a single clone must have been rendered competent to circulate and react to the tumor antigens in vivo. The cytotoxic T cell response appears to play a vital role in the rejection of allografts (47) and may even signal impending rejection (48). However, if the ''desired'' tumor-specific cytotoxic TILs can accumulate within tumors without effecting tumor rejection, one must again emphasize the need for additional factors to achieve tumor rejection.…”

Section: Discussionmentioning

confidence: 99%

In vivoaccumulation of the same anti-melanoma T cell clone in two different metastatic sites

Hishii

Andrews

Boyle

et al. 1997

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

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In a patient with progressing metastatic melanoma, we showed that the same autologous tumorcytolytic CD8 ؉ tumor infiltrating lymphocyte (TIL) clone accumulated in two separate metastatic sites. This clone, which represented three of eight independently derived clones from a tumor deposit on the skin of the abdomen, also represented two of eight clones derived from a skin lesion on the shoulder. This clone could be identified by its use of a unique TCRBV2-nD1n-J1S6 sequence, and could also be detected by single-stranded conformational polymorphism (SSCP) as the dominant TCRBV2-expressing clone among CD8 ؉ TILs propagated from both shoulder and abdominal lesions. Using SSCP analysis, we also demonstrated that this clone was dominant in the fresh tumor tissue and in all TILs in which CD8 ؉ were strongly represented, including several separate but parallel cultures. The SSCP pattern for this clone was not apparent among CD4 ؉ TILs or CD8؉ peripheral blood mononuclear cells. The SSCP analysis of the tumor tissue prior to in vitro culture is an indication that the selection for this anti-tumor cytotoxic T cell clone was a ref lection of its in vivo accumulation. Thus, we provide evidence that melanomas are immunogenic and able to select for cytotoxic antitumor-specific TIL clones that are expanded in vivo and can circulate to accumulate in different tumor sites. However, because these clones were isolated from progressing tumor metastases, the accumulation of these specific cytotoxic T cells was not sufficient to contain tumor growth.It has been shown that the immune response to human melanoma includes cytotoxic T lymphocytes capable of lysing autologous tumor cells in vitro (1-15). Some of the melanoma tumor antigens recognized have been identified and cloned (16)(17)(18)(19)(20)(21)(22). Despite the presence of these cytotoxic lymphocytes, it is evident that the immune response fails to eradicate clinically apparent tumors. Several mechanisms have been proposed to explain tumor escape from immune surveillance, including the loss of HLA alleles needed for T cell recognition (23, 24), as well as other cell surface molecules necessary for induction of T cell activation and proliferation (25).Several laboratories have shown that the tumor infiltrating lymphocytes (TILs) propagated from human melanoma often show restricted T cell antigen receptor (TCR) usage (1,4,12,(26)(27)(28)(29)(30)(31)(32)(33)(34). In some cases it has also been possible to demonstrate that the dominant T cells among the TILs are able to lyse autologous tumors (3,12,35). Still, an unresolved concern has been the lack of unequivocal evidence that the dominant clones isolated in vitro were representative of the in vivo accumulation of these cells within the tumor, rather than a reflection of an in vitro selection. By comparing the TCR usage among the freshly isolated TILs with the TCR which could be sequenced from anti-tumor cytotoxic clones, we addressed the question of whether significant accumulations of melanoma-specific cytotoxic T cells...

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“…In addition, Hassin et al [17] demonstrated that physiologic changes in contraction of cultured rat cardiac myocytes infected with Mingo virus could be induced by lymphocytes sensitized to Mingo virus. Furthermore, the cytotoxic activity of graft-infiltrating lymphocytes correlates with cellular rejection in cardiac transplant patients [18], and acute rejection in heart transplant patients is associated with the presence of donor-specific cytotoxic lymphocytes in the graft but not in the blood [19]. A great deal of interest has therefore been focused on the role of the cytotoxic T lymphocyte in immunemediated myocyte injury duringimmune reactions such as myocarditis or transplant rejection.…”

Section: Effects Of Lymphocytes On Cardiac Myocytesmentioning

confidence: 99%

Effects of cellular elements of the immune response on myocyte function and survival

Barry

1996

Heart Failure Rev

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The immune response is known to be associated with abnormalities of systolic and diastolic cardiac function during cardiac transplant rejection [1-3] and myocarditis [4]. In addition, autoimmunity may be an important contributor to depressed function in idiopathic dilated cardiomyopathy [5,6]. This immune response may impair cardiac performance by altering the function of individual myocytes, by causing myocyte necrosis and thus reducing the mass of functioning myocardium, or by a combination of these effects. The immune response consists of both cellular and humoral components. The cellular component can result in direct interaction of an inflammatory cell with the myocyte, or an indirect effect produced on the myocyte by virtue of secretion of soluble products such as cytokines by the inflammatory cell. The effects of cytokines on myocardial cells are considered at length in other articles in this issue. In this discussion we consider primarily the effects of direct interaction of various inflammatory cells participating in the immune response on myocyte function and survival. Components of the Cellular Inflammatory InfiltrateIt is first appropriate to consider the nature of the cellular infiltrate that occurs in an immune-mediated cardiac inflammation. Tilney and associates [7,8] showed that acutely rejecting cardiac rat allografts contain macrophages (15-25%), lymphocytes (75%), and neutrophils (5%). Of the lymphocytes, approximately 35% were B cells and the remainder were T lymphocytes. The initial infiltrate consists primarily of lymphocytes, with infiltration by a larger number of macrophages and neutrophils occurring with more complete rejection. Acute murine viral myocarditis is also associated with an infiltrate of macrophages and lymphocytes, including natural killer (NK) cells [9]. Recent work from our laboratory with the murine heterotopic mouse heart transplant model [10] demonstrated that the heart-infiltrating cell population consists of 44% lymphocytes, 30% macrophages, and 20% neutrophils 5-7 days after transplantation. Further studies in our laboratory have documented that the function of the transplanted heart is significantly depressed at this point [11]. We will therefore consider which components of this immune infiltrate could be responsible for cardiac depression during immune-mediated injury and the mechanisms involved. The work to be described will be focused primarily on the transplant rejection model, although, as mentioned earlier, it is very likely that similar mechanisms are involved in the myocardial functional depression noted during myocarditis, and possibly during autoimmune injury associated with idiopathic dilated cardiomyopathy. Effects of Lymphocytes on Cardiac MyocytesWe will first consider the effects oflymphocytes on myocyte function and survival. There are several types of lymphocytes that are involved in immune reactions. Cellular responses are mediated by T lymphocytes. Helper T lymphocytes (HTL; CD4 ÷) recognize endocytosed peptides that are bound to class II MHC mol...

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Cytotoxic activity of graft-infiltrating lymphocytes correlates with cellular rejection in cardiac transplant patients

Cited by 17 publications

References 7 publications

Cytomegalovirus hyperimmunoglobulin: mechanisms in allo‐immune response in vitro

Cytomegalovirus hyperimmunoglobulin: mechanisms in allo‐immune response in vitro

In vivoaccumulation of the same anti-melanoma T cell clone in two different metastatic sites

Effects of cellular elements of the immune response on myocyte function and survival

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