scholarly journals HLA restriction of human cytotoxic T lymphocytes specific for influenza virus. Poor recognition of virus associated with HLA A2.

1978 ◽  
Vol 148 (6) ◽  
pp. 1458-1467 ◽  
Author(s):  
A McMichael

Cytotoxic T lymphocytes (CTL), specific for influenza A/X31 virus, were generated from human peripheral blood lymphocytes. These CTL lysed target cells that were infected with the same virus and that shared HLA A or B locus antigens. Minimal lysis was observed when HLA-D antigens were shared. Not all HLA A and B antigens were equally effective. Efficient lysis of target cells was seen when HLA A1, A3, B7, B8, B27 and BW21 were shared with the CTL, but when HLA A2 was the only shared antigen lysis was usually minimal. This deficiency in CTL function associated with HLA A2 was not absolute. It is suggested that the function of this antigen might be influenced by other surface molecules on the cell and in particular the other HLA products.

Author(s):  
Darya B. Nizheharodava ◽  
Galina A. Ksendzova ◽  
Aliaksei G. Sysa ◽  
Mariya Yu. Yurkevich ◽  
Maryna V. Labai ◽  
...  

Derivatives of 2-amino-4,6-di-tert-butylphenol exhibit antiviral properties and radical regulatory activity against various types of organic radicals which determines the actuality of their further investigation. But the question of aminophenol derivatives immunomodulatory activity remains open. In this regard, the aim of the study was to assess the effects of 2-amino-4,6-di-tert-butylphenol derivatives on the viability and functional potential of human peripheral blood lymphocytes. As a result of the studies, it was shown that aminophenol compounds at concentrations of 10–5–10–7 mol did not exert a toxic effect while at a concentration of 10–4 mol showed a cytotoxic effect due to the induction of secondary necrosis. Compounds N-(2-hydroxy-3,5-di-tert-butylphenyl)-4-methylbenzenesulfonamide and 2,4-di-tert-butyl-6-morpholinophenol at a concentration of 10–6 mol stimulated the extracellular production of α-interferon by peripheral blood mononuclear cells and intracellular production of γ-interferon by CD3+T-lymphocytes. An immunosuppressive effect (more than 50 %) of N-(2-hydroxy-3,5-di-tert-butylphenyl)-4-methylbenzenesulfonamide and 2,4-di-tert-butyl-6-morpholinophenol compounds at a concentration of 10–5 mol was revealed to the mitogen-induced proliferation of T-lymphocytes.


1992 ◽  
Vol 78 (2) ◽  
pp. 79-86 ◽  
Author(s):  
Qi Chen ◽  
Peinan Sun ◽  
Ignazia Prigione ◽  
Hong Xie ◽  
Silvano Ferrini

In an attempt to construct bispecific monoclonal antibodies (bimAbs) able to target cytotoxic T lymphocytes against human hepatoma cells, an HGPRT-deficient mutant of the Hepama-6 hybridoma, which produces an antihuman-hepatoma mAb, was directly fused with splenocytes from Balb/C mice immunized by a polyclonal cytotoxic T-cell line. Hybrid hybridomas were selected in HAT medium, and their supernatants were directly screened for the ability to induce IL-2-cultured cytotoxic T lymphocytes to kill hepatoma cells in a 51Cr-release assay. The selected hybrid hybridoma, termed DQ-33, secretes a bimAb, which reacts with a CD3-associated determinant. When resting peripheral-blood lymphocytes were used as effector cells, virtually no cytolytic activity could be induced by DQ-33, whereas phytohemagglutinin-activated lymphocytes that had been expanded in vitro in IL-2-containing medium could be efficiently targeted against hepatoma cells. Targeting by DQ-33 bimAb was analyzed on different subsets of IL-2-cultured lymphocytes. It was evident that CD+4–8+ TCRα/β+ and CD3+4–8-TCRγ/δ+ lymphocytes were efficiently induced by bimAb to lyse human hepatoma cells, whereas no induction of cytolysis could be observed when CD3 + 4+8-TCRα/β+ cells were used as effectors. DQ-33 bimAb was also able to induce lymphokine secretion (IL-2, GM-CSF and TNF-α) by all the different subsets of lymphocytes analyzed in the presence of target cells expressing the relevant antigen, independent of the expression of cytolytic activity.


1985 ◽  
Vol 162 (5) ◽  
pp. 1720-1725 ◽  
Author(s):  
A Yamada ◽  
J F Young ◽  
F A Ennis

We have tested the ability of the c13 protein, which is a hybrid protein of the first 81 amino acids of the viral nonstructural protein (NS1) and the HA2 subunit of viral hemagglutination produced in E. coli, to render target cells susceptible to the lytic activity of influenza virus-specific cytotoxic T lymphocytes (CTL). The results showed that P815 cells coated with c13 protein were lysed by PR8 virus-induced secondary CTL derived from BALB/c mice. Cold-target inhibition tests clearly demonstrated that c13 protein-coated P815 cells were recognized by an H1 subtype-specific CTL population. Furthermore, PR8 virus-induced CTL derived from C3H mice did not lyse c13 protein-coated P815 cells, suggesting that c13 protein was recognized by CTL in conjunction with H-2d products. These findings suggest that this protein interacts with the cellular plasma membrane and makes target cells recognizable by H-2-restricted, influenza virus subtype-specific CTL.


1987 ◽  
Vol 166 (5) ◽  
pp. 1536-1547 ◽  
Author(s):  
C R Verret ◽  
A A Firmenich ◽  
D M Kranz ◽  
H N Eisen

A cytotoxic T lymphocyte (CTL) characteristically kills target cells one after the other by releasing toxic granules that contain one or more cytolytic components. To determine how CTLs avoid destroying themselves when they release granules and lyse target cells, 7 murine CD8+ CTL cell lines were compared with 19 other cell lines for susceptibility to lysis by the isolated toxic granules. Murine CD8+ CTLs were clearly the most resistant cells: granules did not lyse them even after they were exposed to azide, cyanide, and 2-deoxyglucose, conditions that were found to enhance the susceptibility of all the other cells tested, including other T cells. Thus, resistance of CD8+ CTLs to cytotoxic granules appears to be independent of cellular ATP. To reconcile these findings with other observations that, under some circumstances, CTLs can be lysed by other CTLs, we suggest a model in which a CTL releases only a limited proportion of its toxic granules at each antigen-specific encounter with a target cell; the amount released is sufficient to kill most target cells but to leave the CTL undamaged and with enough granules to attack other target cells.


1975 ◽  
Vol 61 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Sergio Tognella ◽  
Giovanni Mantovani ◽  
Gennaro S. Del Giacco ◽  
Paolo E. Manconi ◽  
Letizia Cengiarotti ◽  
...  

The PHA-resposiveness of normal and Hodgkin patient human peripheral blood lymphocytes has been studied before and after incubation with Hodgkin cytotoxic sera. The following conclusions have been reached: (a) Hodgkin cytotoxic serum is capable of decreasing the PHA-responsiveness of normal lymphocytes and of furtherly impairing the already defective PHA-responsiveness of Hodgkin lymphocytes. (b) The impaired PHA-responsiveness can be restored to the original levels by eluting the cytotoxic antibody. Control experiments in which normal and Hodgkin lymphocytes were put in contact with normal and Hodgkin non-cytotoxic serum showed no decrease of PHA-responsiveness. These data are in agreement with the hypothesis that the presence of serum cytotoxin is at least partly responsible for the immuno-incompetence of T-lymphocytes characteristic of Hodgkin's disease.


2015 ◽  
Vol 35 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Jin Sik Kim ◽  
Kyung Seuk Song ◽  
Il Je Yu

Carbon nanotubes (CNTs) have been introduced recently as a novel carrier system for both small and large therapeutic molecules. Biotin-functionalized single-wall CNTs have been conjugated with the anticancer agent taxoid using a cleavable linker, and multiwall carbon nanotubes (MWCNTs) conjugated with iron nanoparticles have been efficiently loaded with doxorubicin. 1 , 2 The MWCNTs are effective transporters for biological macromolecules and drugs to target cells and tissues, thereby attracting the attention of the biomedical industry. 3 – 7 Administrating MWCNTs for medical application invariably involves intravenous administration and ultimate contact with human peripheral blood lymphocytes (HPBLs), yet toxicological studies on the effect of MWCNTs on HPBLs are lacking. Accordingly, this study evaluated the cytotoxic and genotoxic effects of MWCNTs on healthy male HPBLs. Healthy male HPBLs were treated with MWCNTs at 3 different concentrations (12.5, 25, and 50 μg/mL) for 48 hours. Under these conditions, the MWCNTs induced significant cell growth retardation, DNA damage, and cytotoxicity. The MWCNT-treated HPBLs also exhibited an increased intracellular reactive oxygen species level during the experimental period, which leads to cell damage and death, proliferation inhibition, DNA damage, and an inflammatory response.


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