HLA-D region-associated determinants serve as targets for human cell-mediated lysis.

Feighery, Conleth; Šťastný, Peter

doi:10.1084/jem.149.2.485

Cited by 73 publications

(28 citation statements)

References 22 publications

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“…5a). This finding differs from observations in humans and mice, in that CML reactivity should not be generated in lymphocytedefined and serologically defined identical pairs, although there are isolated observations to the contrary (33,34 (Fig. 5b), in support of observations in our previous studies (35,36).…”

Section: Methodscontrasting

confidence: 56%

Long-Term Study of Vascularized Free-Draining Intraperitoneal Pancreatic Segmental Allografts in Beagle Dogs

Kyriakides¹,

Rabinovitch²,

Mintz³

et al. 1981

J. Clin. Invest.

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A B S T R A C T The purpose of the present study was to evaluate the significance of immunogenetic factors on the survival of pancreatic allografts in beagle dogs. Donors and recipients were leukocyte antigen (DLA)-typed and mixed lymphocyte culture (MLC)-tested. Recipients were made diabetic by total pancreatectomy and immediately implanted intraperitoneally with a vascularized, free-draining (duct unligated) pancreatic segmental (FDPS) allograft. Two groups of dogs were studied. In group I consisting of donor-recipient littermates, recipients were immunosuppressed with prednisone and azathioprine (n = 16 dogs), or not immunosuppressed (n = 4). In group II, recipients were made specifically unresponsive by total body radiation, autologous marrow implantation, and kidney transplantation from DLA-MLC identical donors, 1 yr before FDPS transplantation from the corresponding original kidney donors.Survival of the FDPS grafts in group I was inversely related to pretransplant MLC reactivity, irrespective of DLA genotyped match between donor and recipient. Thus, immunosuppressed high MLC reactors (n = 8) rejected FDPS grafts between 7 and 14 d, whereas immunosuppressed low MLC reactors (n = 8) accepted grafts for 25 to 260+ days, and nonimmunosuppressed low MLC reactors (n = 4) accepted grafts for 9-55 d. Rejection (hyperglycemia) of FDPS grafts was sudden, permanent, and unpredictable despite weekly intravenous glucose tolerance tests with measurements of glucose disappearance rates and serum insulin responses. Nevertheless, serial in vitro cell-mediated

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Section: Methodscontrasting

confidence: 56%

Long-Term Study of Vascularized Free-Draining Intraperitoneal Pancreatic Segmental Allografts in Beagle Dogs

Kyriakides¹,

Rabinovitch²,

Mintz³

et al. 1981

J. Clin. Invest.

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“…Resolution of this question was particularly important in view of the recent demonstration that polymorphisms at the HLADRw locus can indeed be recognized by allospecific cytotoxic T cells, a fact which only became apparent with the use of suitable HLA-DRw antigen-bearing target cells [19]. In the present experiments, the slight inhibition of EB virus-transformed target cell lysis which was on occasions observed in the presence of saturating concentrations of monoclonal antibodies CA2 and TDR31.1, binding common determinants on all HLA-DRw molecules, seemed to be a nonspecific effect (perhaps mediated by the antibodies against the effector T cells themselves) for it was equally apparent whether cytotoxicity was being assayed against the autologous cell line or against an HLA-A, B, C antigen-matched, HLA-DRw antigen-mismatched allogeneic cell line (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic T cell recognition of Epstein‐Barr virus‐infected B cells. II. Blocking studies with monoclonal antibodies to HLA determinants

et al. 1981

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Monoclonal antibodies specifically binding common determinants on all HLA-A, B anc C antigen molecules blocked the lysis of EB virus-transformed target cells by EB virus-specific cytotoxic T cells reactivated in vitro. Blocking was mediated through binding of the antibodies to the target rather than to the effector cells and was maximal (75 to 85% inhibition of lysis) at saturating antibody concentrations. A similar blocking effect was also shown by a monoclonal antibody binding to beta 2-microglobulin, a molecule physically associated with HLA-A, B and C antigens on the target cell surface, but not by a monoclonal antibody binding to the non-HLA-associated leukocyte-common antigen. Saturating concentrations of monoclonal antibodies specific for common determinants on all HLA-DRw antigen molecules either had no effect at all upon EB virus-specific T cell cytotoxicity or caused a slight, but nonspecific, inhibition. The results demonstrate unequivocally that HLA-A, B and C antigens on the target cell surface are indeed the polymorphic elements which impose genetic restriction upon EB virus-specific cytotoxic T cell function.

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“…They include the production of cytokines, most notably IFN-γ and TNF (Hung et al, 1998; Pardoll and Topalian, 1998) and through direct cytolytic activity (Trapani and Smyth, 2002) that is mediated by degranulation of cytotoxic granules containing toxic effector molecules (i.e., perforin and granzyme) or ligation of the Fas (also known as CD95)/Fas Ligand (FasL; also known as CD95L) apoptotic killing pathway (Green and Ferguson, 2001). Cytolytic CD4 T cells possessing such cytotoxic activity have been described in peripheral blood of both healthy and virally infected individuals (Feighery and Stastny, 1979; Appay et al, 2002; van Leeuwen et al, 2004; Casazza et al, 2006; Stuller and Flano, 2009; Nemes et al, 2010; Stuller et al, 2010). Phenotypic analysis has shown that they are CD45RO + , CCR7 − , CD27 − , and CD28 − and shown to possess high levels of the cytolytic effector molecules granzyme A, granzyme B and perforin (Appay et al, 2002; Casazza et al, 2006) suggesting that these cells are antigen-experienced and terminally differentiated CD4 effector cells.…”

Section: Cd4 Effector T Cell Subsetsmentioning

confidence: 99%

Expanding Roles for CD4 T Cells and Their Subpopulations in Tumor Immunity and Therapy

Dobrzanski¹

2013

Front. Oncol.

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The importance of CD4 T cells in orchestrating the immune system and their role in inducing effective T cell-mediated therapies for the treatment of patients with select established malignancies are undisputable. Through a complex and balanced array of direct and indirect mechanisms of cellular activation and regulation, this functionally diverse family of lymphocytes can potentially promote tumor eradication, long-term tumor immunity, and aid in establishing and/or rebalancing immune cell homeostasis through interaction with other immune cell populations within the highly dynamic tumor environment. However, recent studies have uncovered additional functions and roles for CD4 T cells, some of which are independent of other lymphocytes, that can not only influence and contribute to tumor immunity but paradoxically promote tumor growth and progression. Here, we review the recent advances in our understanding of the various CD4 T cell lineages and their signature cytokines in disease progression and/or regression. We discuss their direct and indirect mechanistic interplay among themselves and with other responding cells of the antitumor response, their potential roles and abilities for “plasticity” and memory cell generation within the hostile tumor environment, and their potentials in cancer treatment and immunotherapy.

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HLA-D region-associated determinants serve as targets for human cell-mediated lysis.

Cited by 73 publications

References 22 publications

Long-Term Study of Vascularized Free-Draining Intraperitoneal Pancreatic Segmental Allografts in Beagle Dogs

Long-Term Study of Vascularized Free-Draining Intraperitoneal Pancreatic Segmental Allografts in Beagle Dogs

Cytotoxic T cell recognition of Epstein‐Barr virus‐infected B cells. II. Blocking studies with monoclonal antibodies to HLA determinants

Expanding Roles for CD4 T Cells and Their Subpopulations in Tumor Immunity and Therapy

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