The cytotoxic response to murine cytomegalovirus: requirements for the generation of MCMV-specific target cells

1987 ◽  
Vol 65 (2) ◽  
pp. 173-182 ◽  
Author(s):  
VG Sinickas ◽  
RB Ashman ◽  
RV Blanden
Keyword(s):  
Murine Cytomegalovirus ◽  
Target Cells ◽  
Specific Target ◽  
Cytotoxic Response

scholarly journals In vitro induction of T-lymphocyte-mediated cytotoxicity by infectious murine type C oncornaviruses.

1979 ◽  
Vol 150 (6) ◽  
pp. 1367-1382 ◽  
Author(s):  
T Taniyama ◽  
H T Holden
Keyword(s):  
Uv Light ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Target Cells ◽  
Induction Phase ◽  
Effector Cells ◽  
Cytotoxic Response ◽  
Culture Cells ◽  
Murine Sarcoma Virus

We have developed a system to induce oncornavirus-specific secondary cytotoxic response in vitro. When Moloney strain of murine sarcoma virus-immune spleen cells were cultivated with purified infectious Moloney murine leukemia virus (M-MuLV) or with supernates of tissue culture cells containing infectious virus, a virus-specific secondary cytotoxic response directed against type-specific determinant(s) of M-MuLV was generated in vitro, as determined by a 4-h 51Cr-release assay. The effector cells were susceptible to the treatment with anti-Thyl.2 plus complement, but were unrelated to natural killer cells (NK), because they could not lyse some target cells specific for M-MuLV in both the induction phase and the interaction between effector cells and target cells. Furthermore, a product of the env gene of M-MuLV, perhaps gp70, appeared to be responsible for this response, because viruses with recombinations in the env gene between ecotropic M-MuLV and a xenotropic virus failed to induce a response. When infectious M-MuLV was exposed to UV-light at different doses, the ability of UV-treated M-MuLV to induce a secondary cytotoxic response decreased in parallel with infectivity, indicating that infectivity was necessary for the induction of this response.

scholarly journals THYMOCYTES FROM MICE IMMUNIZED AGAINST AN ALLOGRAFT RENDER BONE-MARROW CELLS SPECIFICALLY CYTOTOXIC

1972 ◽  
Vol 135 (1) ◽  
pp. 150-164 ◽  
Author(s):  
C. K. Grant ◽  
G. A. Currie ◽  
P. Alexander
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Target Cells ◽  
Cytotoxic Action ◽  
Specific Target ◽  
C57bl Mice ◽  
Specific Increase ◽  
Spleen And Lymph Nodes ◽  
Marrow Cells

Thymocytes from C57BL mice immunized with the DBA/2 lymphoma L5178Y exert in vitro an immunologically specific cytotoxic action against the target cells in the presence of bone-marrow cells. Neither the nonimmune bone marrow nor the immune thymocytes are by themselves cytotoxic. The cells in the bone marrow which take part in the cytotoxic action adhere to glass and are sensitive to anti-macrophage serum. These bone-marrow cells can also be rendered specifically cytotoxic by exposure to the supernatant obtained from a culture of immune thymocytes with the specific target cells. The thymocytes before they are confronted with the specific target cells are very radiosensitive; however, on coming into contact with the target cells, an immunologically specific increase in RNA synthesis occurs and thereafter the thymocytes' capacity to render bone-marrow cells cytotoxic is relatively radioresistant. Two classes of immune lymphocytes occur in mice immunized with allogeneic cells, those that are capable of killing target cells directly and those that produce a factor capable of rendering macrophages (or monocytes) specifically cytotoxic. In the thymus of immune animals only the latter are found while both categories are present in the spleen and lymph nodes of immune animals.

scholarly journals Correlation between CD8 dependency and determinant density using peptide-induced, Ld-restricted cytotoxic T lymphocytes.

1991 ◽  
Vol 173 (4) ◽  
pp. 849-858 ◽  
Author(s):  
M A Alexander ◽  
C A Damico ◽  
K M Wieties ◽  
T H Hansen ◽  
J M Connolly
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Effector Function ◽  
Murine Cytomegalovirus ◽  
Target Cells ◽  
Spleen Cells ◽  
Fourfold Increase ◽  
Quantitative Correlation ◽  
Primary Sensitization ◽  
Better Than

We have taken advantage of some unique properties of H-2Ld to investigate the determinant density requirements for cytotoxic T lymphocyte (CTL) priming versus effector function and to correlate the determinant density requirements with CD8 dependency. In a previous study (Lie, W.-R., N. B. Myers, J. Gorka, R. J. Rubocki, J. M. Connolly, and T. H. Hansen. 1990. Nature [Lond.]. 344:439), we demonstrated that culturing normal cells with peptides known to be restricted by H-2Ld led to a two- to fourfold increase in surface Ld expression. In the present study, we demonstrate the generation of Ld-restricted, peptide-specific in vitro primary CTL by culturing spleen cells with murine cytomegalovirus or tum- peptide at concentrations previously shown to result in maximum induction of Ld expression. Target cells can be sensitized for recognition by these CTL with lower dose of peptide than are required for the primary sensitization. This demonstrates differences in the determinant density requirements for priming versus effector function. The in vitro primary CTL generated with peptide can weakly lyse target cells that express the determinant endogenously, and CTL lines and clones capable of strong lysis of endogenous expressors are easily obtained. In both cases, target cells treated with exogenous peptide are lysed better than target cells expressing antigen endogenously. This suggested that there are differences in the determinant density of peptide-fed versus endogenous targets. This interpretation was substantiated when it was observed that the level of lysis of target cells expressing endogenous determinants correlated inversely with the amount of peptide required to sensitize targets for recognition by various tum- -specific CTL clones. Furthermore, simultaneous titration of both the peptide used to treat target cells and the antibody to CD8 revealed that the various CTL clones analyzed displayed widely disparate CD8 dependencies. In each case, the CD8 dependency correlated inversely with the determinant density requirement. Therefore, CD8 dependency of CTL is relative, but shows an absolute and quantitative correlation with their dependency on determinant density. These findings suggest that under physiologic conditions, where only low determinant densities are likely to be encountered, all CTL clones will show at least partial CD8 dependency.

scholarly journals Hemagglutinin-specific cytotoxic T-cell response during influenza infection.

1977 ◽  
Vol 146 (3) ◽  
pp. 893-898 ◽  
Author(s):  
F A Ennis ◽  
W J Martin ◽  
M W Verbonitz
Keyword(s):  
T Cell ◽  
Target Cell ◽  
Cell Response ◽  
Influenza A ◽  
Influenza Infection ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Cervical Lymph Nodes ◽  
Cytotoxic Response

Specific cytotoxic thymus-derived (T) lymphocytes were detected in the cervical lymph nodes and spleen during influenza infection of mice. The cytotoxic T cells can distinguish target cells infected with different influenza A subtypes. Infection with parent viruses and their recombinant progeny possessing the hemagglutinin of one parent and the neuraminidase of the other demonstrated that significant cytotoxicity occurred only when the hemagglutinin of the immunizing viruses was the same as that of the virus used to infect the target cell. In addition to this specific cytotoxic response to the major surface antigen, a cross-reactive response could be detected when the relatively nonpermissive L cell was used as the target cell. These results indicate there is a specific cytotoxic T-cell response to the surface hemagglutinin, and a cross-reactive cytotoxic response, not directed to the hemagglutinin, during influenza infection. The cytotoxic T-cell response specific for the hemagglutinin antigen may play an important role in in vivo immunity to influenza.

scholarly journals A nonstructural polypeptide encoded by immediate-early transcription unit 1 of murine cytomegalovirus is recognized by cytolytic T lymphocytes.

1987 ◽  
Vol 166 (1) ◽  
pp. 289-294 ◽  
Author(s):  
U H Koszinowski ◽  
G M Keil ◽  
H Schwarz ◽  
J Schickedanz ◽  
M J Reddehase
Keyword(s):  
Regulatory Protein ◽  
Antigen Expression ◽  
Transcription Unit ◽  
Immediate Early ◽  
Murine Cytomegalovirus ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Gene Encoding ◽  
Dna Coding ◽  
Early Transcription

We have constructed target cells by cotransfection of the MHC gene Ld and fragments of murine cytomegalovirus (MCMV) DNA coding for nonstructural immediate-early (IE) proteins. Transfectants were tested by using CTL clone IE1 with specificity for an IE epitope presented in association with Ld. Data show that clone IE1 recognizes a product of the ie1 transcription unit of MCMV, and that its specificity is shared by approximately 25% of polyclonal IE-specific CTL. The results provide the first definite evidence that expression of a herpes virus IE gene encoding a regulatory protein gives rise to antigen expression detectable by specific CTL.

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