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Biomedical subjects

G L Ada

Publications and source records attributed to G L Ada.

At least 73 records · Page 4Linked to original sources
PubMed1980

Specificity, Ly phenotype, and H-2 compatibility requirements of effector cells in delayed-type hypersensitivity responses to murine influenza virus infection.

Delayed-type hypersensitivity (DTH) to infectious and to noninfectious (UV-irradiated) influenza A viral preparations was measured in mice by the increase in footpad swelling 24 h after injection of the eliciting virus. DTH mice sensitized with noninfectious virus was elicited only by virus that shared hemagglutinin specificity with the sensitizing virus, whereas footpad injection of a given A-strain virus (A/WSN) could elicit DTH in mice sensitized with a variety of infectious A-strain viruses, including some not sharing hemagglutinin or neuraminidase specificities. The effector T cells generated in mice sensitized with either form of virus were sensitive to anti-Ly 1.1 serum and complement, but not to anti-Ly 2.1 serum and complement. Adoptive transfer of DTH was H-2 restricted. With spleen cells from mice sensitized subcutaneously with either infectious or noninfectious virus, sharing of the IA region was both necessary and sufficient for successful transfer to occur. Cells recovered from infected mouse lungs, and secondary effector cells generated in vitro transferred DTH if injected into the footpad with the eliciting virus. The effector cells had the Ly 1 phenotype, and, in both cases, the cells were I restricted. These results contrast with earlier findings that transfer of DTH to lymphocytic choriomeningitis virus infection required K- or D-region sharing between donor and recipient. Thus, the earlier hypothesis that multiplying infectious agents such as viruses would "alter" K- or D-coded, rather than I-coded, structures is not generally correct.

Animals↗
PubMed1980

Selective suppression of the cytotoxic T cell response to influenza virus in mice.

Mice injected with inactivated (UV light-irradiated) influenza virus produce specific antibody, become sensitized for a delayed-type hypersensitivity reaction, but do not generate specific cytotoxic T (Tc) cells. If injected 4-5 days later with infectious virus, the formation of Tc cells is suppressed by > 90%. If A strain viruses are used, the suppression observed is cross-reactive within A strain viruses but does not extend to B/LEE or to Sendai virus. Serum from mice injected with UV-irradiated virus contains antibodies which on adoptive transfer can inhibit Tc cell formation when infectious homologous virus is used to challenge the recipients. Spleen cells from the same mice, upon adoptive transfer, also inhibit (50-70%) Tc cell formation if transferred within 24 h of injection of infectious virus, and the specificity pattern observed is cross-reactive within A strains. The activity of the cells mediating suppression is destroyed by monospecific anti-Thy-1.2 antibody and complement. The immune cells require I region sharing between donor and recipient mice for their suppressor activity to be effective. (There is also a partial requirement for K, D region sharing, but the possible rejection of transferred cells is not excluded.) Dilution assays in which clonal expansion of Tc precursors is used to estimate their frequency and the presence of T helper (Th) cells indicate that suppressed mice possess Tc precursors and primed cells which, upon restimulation, act as Th cells. Furthermore, injection of irradiated Th cells with inactivated virus does not significantly reduce the ensuing suppression.

Animals↗
PubMed1980

Generation of influenza virus specific delayed type hypersensitivity T cells in vitro. Secondary effector cells.

When spleen cells from mice injected 3 weeks or more previously with influenza A virus (responder cells) are mixed with normal spleen cells exposed 1 h previously to influenza A virus (stimulator cells) and the mixture cultivated at 37 degree for 5-6 days, the surviving cell population contains effector T cells (Td) which can mediate delayed type hypersensitivity reactions. If infectious virus is used to prime both the donor mice and to infect the stimulator cells, the cell population also contains cytotoxic T cells (Tc). In this case, both Tc and Td have similar specificity patterns, as cells raised to one sub-type A virus are cross-reactive to other A strain viruses but not to Sendai virus. If non-infectious virus is used to immunize the donor mice, Td but not Tc are generated and these cells are specific for the sub-type A virus used in the original immunization. Both preparations of Td are Lyl+23- and require IA sharing of donor and recipient mice for transfer DTH activity to be successful. Td cells produced this way are similar to those produced in vivo except they may have different migratory properties and must be injected directly into the footpad for DTH activity to be elicited. In such transfers, H-2 restriction can be clearly demonstrated if the challenging antigen is injected into the footpad some hours before the injection of cells.

Animals↗
PubMed1980

Production of DTH in the mouse to influenza virus: comparison with conditions for stimulation of cytotoxic T cells.

The kinetics of sensitization and elicitation of delayed-type hypersensitivity in mice to both infectious and non-infectious preparations of influenza virus was found to be similar to that of some protein antigens and to other viruses. Sensitization was achieved without added adjuvant. Maximum DTH was elicited in the footpad 6 days after sensitization. Adoptive transfer experiments showed that the effector cells were in the Ig-negative fraction of the spleen and were sensitive to anti-theta and complement. A comparison was made of conditions for the generation of DTH activity with cytotoxic T cells. The route of inoculation was important. With a high dose (10(3) HAU) of virus, subcutaneous inoculation was the most efficient and intravenous injection the least efficient for sensitizing for DTH, whereas the reverse was found for cytotoxic T-cell generation. Second, treatment of mice with cyclophosphamide (Cy) had differential effects. Preinjection of a large dose (200 mg/kg) into mice 2 days before sensitization with virus resulted in an increase in the DTH response and a 90% reduction in cytotoxic T-cell activity in the spleens of the treated mice. The Cy-injected mice had reduced (70%) anti-haemagglutinin levels compared with the controls. This may be the explanation for the enhanced DTH response, since transfer of specific antibody to sensitized mice before injection of the eliciting virus substantially reduced the DTH response. Pretreatment with Cy did not affect the generation of DTH effector cells, since spleen cells from these and control mice had similar levels of activity.

Animals↗
PubMed1980

Cells mediating delayed-type hypersensitivity in the lungs of mice infected with an influenza A virus.

Effector cells that demonstrate delayed-type hypersensitivity (DTH) on transfer with antigen to naive mice can be recovered from the lungs of mice inoculated intranasally 6 days earlier with a lethal dose (usually 5x10(1)EID50) of influenza A virus. The activity recovered was proportional to the dose of virus instilled intranasally and the extent of lung consolidation observed. Active cells could also be recovered from the draining lymph nodes and from the peripheral blood. The effector cells were identified as T lymphocytes of Ly 1 phenotype and required I-region sharing between donor and recipient for activity to be elicited. They were cross-reactive within the A group of influenza viruses. Two experiments are reported in which immune cell preparations that expressed DTH activity but had very little cytotoxic T cell activity were transferred to mice inoculated 1 or 2 days earlier with a lethal dose of virus. The mice were not protected from death, and in both experiments, the recipient mice died more rapidly than the controls. These results contrast with earlier results in which cell preparations with high cytotoxic T-cell activity were shown to protect recipient infected mice from death.

Animals↗
PubMed1980

Two T-cell populations mediate delayed-type hypersensitivity to murine influenza virus infection.

Two classes of T lymphocytes can mediate delayed-type hypersensitivity (DTH) to influenza virus in the mouse. If non-infectious virus preparations are used to sensitize for or to elicit a DTH response, the effector cells are found to be Ly-1-positive and are I-region-restricted. If infectious virus is used both to sensitize for and to elicit the reaction, a second set of effector cells is also directed, which are Ly-2,3-positive and are D- or K,D-region-restricted. The latter cells are cross-reactive within the A strains of influenza viruses, and pretreatment of the mice with high doses of cyclophosphamide markedly decreases their generation in the spleens of sensitized mice, suggesting that the cells that demonstrate DTH activity in vivo may also have cytotoxic activity in vitro.

Animals↗
PubMed1979

The measurement of haemagglutinin and matrix protein present on the surface of influenza virus infected P815 mastocytoma cells.

A thermodynamic approach has been used to measure the amount of haemagglutinin and matrix protein expressed at the surface of P815 cells infected for periods between 4.5 and 11 h with either WSN (H0N1) or JAP (H2N2) strains of type A influenza virus. This involved measuring the interaction of different concentrations of labelled (Fab)2 preparations of specific antibody with normal and infected cells. Assuming that one molecule of (Fab)2 bound to one molecule of antigen, values for the number of molecules of antigen/infected cell ranged from 7.6 X 10(5) to 1.7 X 10(7) for haemagglutinin and 1.3 X 10(5) to 1.1 X 10(6) for matrix protein. The ratio of haemagglutinin/matrix protein was lower for WSN-infected cells (1.7) than for JAP-infected cells (10). The same reagents were reacted with three purified A type virions; WSN, JAP and Port Chalmers (H3N2). Each preparation bound anti-matrix protein (Fab)2 though the value for haemagglutinin/matrix protein was much higher (66) than for infected cells and suggested that a virion may have a small number (about 12) of matrix protein molecules exposed though it was not excluded that the matrix protein detected was exposed only on damaged virions. Pre-treatment of infected cells with unlabelled reagent (anti-haemagglutinin) reduced the subsequent binding of the same labelled reagent but not the binding of the labelled matrix protein reagent and vice versa, suggesting that the haemagglutinin and matrix protein were not very close to each other on the cell surface.

Antigen-Antibody Complex↗
PubMed1979

The effect of specific antibody on the generation of cytotoxic T lymphocytes and the recovery of mice from influenza virus infection.

A study has been made of the effect of humoral antibody on the generation of specific cytotoxic T cells (Tc) in the spleen or lungs after intravenous injection or intranasal inoculation of infectious influenza virus. Antibody injected before or at the same time as virus inhibited completely the generation of Tc in the spleen. If injected 1 h after virus, the inhibition was reduced by 50%, and little inhibition occurred if antibody was injected 6 h after virus. This suggested that antibody failed to influence Tc generation once infection of stimulating cells had occurred. Antibody injected intravenously 24 h after intranasal inoculation of virus into normal mice did not affect the level of cytotoxic activity present in the lungs, and trace amounts only (less than 1 log10 EID50) could be recovered from the lungs at 6 days. As there is a high titre (greater than 6 log10 EID50) of infectious virus in the lungs of mice 24 h after infection, this represents a very efficient control mechanism. The same protocol carried out with athymic mice gave only a partial clearance (c. 3 log10 EID50) of virus in the lungs. It was suggested that a major role of humoral antibody was to limit infection by the virus, and in this respect it complemented the action of Tc.

Animals↗
PubMed1978

Cytotoxic T cells in the lungs of mice infected with an influenza A virus.

Cytotoxic T cells are present in the lungs and the bronchoalveolar washings of mice infected intravenously (i.v.) or intranasally (i.n.) with live influenza A/WSN virus. After i.v. injection, cytotoxic T cell activity in both spleens and lungs reaches a peak at 6 days when the level of infectious virus recovered from the lungs falls sharply and the mice do not die. If a lethal dose of virus is given intranasally, very high levels of virus appear rapidly in the lungs, and the development of lung consolidation follows slightly behind the appearance of cytotoxic T cells there. When a non-lethal dose of virus is given intranasally, lower levels of virus are found in the lung and the appearance of cytotoxic T cells is delayed. These results suggest that the cytotoxic T cells play a protective role if the level of virus in the lungs does not reach very high levels. After injection of antithymocyte serum, the subsequent level of cytotoxic T cell activity in the lungs was greatly reduced, suggesting that the T cells recovered in lungs had at an earlier stage been circulating cells. However, splenectomized mice develop high levels of cytotoxic T cell activity, after intranasal infection of mice, indicating that the spleen did not contribute substantially to the T cells recovered in the lungs.

Animals↗
PubMed1978

The recovery of mice from influenza virus infection: adoptive transfer of immunity with immune T lymphocytes.

Transfer of primary or secondary influenza-immune spleen cells to mice infected intranasally with influenza virus resulted in a significant clearance of virus from the lungs and the protection of the recipients from death. The antiviral activity was associated only with intact, viable cells and was not due to carryover of virus. The effector cell population responsible for the antiviral effect was shown to be T cells. Thus, the removal of adherent, phagocytic and Ig+ cells did not affect the antiviral activity, whereas it was destroyed with antitheta serum and complement. Antiviral activity was specific and was best expressed if the virus used to infect the recipients and to generate immune cells was the same strain. Further work will be necessary to define rigorously the role of different viral antigens in cell-mediated immune response to influenza virus infection.

Animals↗
PubMed1978

The recovery of mice from influenza A virus infection: adoptive transfer of immunity with influenza virus-specific cytotoxic T lymphocytes recognizing a common virion antigen.

Mice inoculated intranasally with infectious influenza virus of a given A strain were adoptively transferred 24 h later with preparations of secondary influenza virus-immune T cells generated either in vitro or entirely in vivo. The immune cells were raised during infection with homologous or heterologous A strain influenza viruses or with a type B virus. The greatest antiviral effect, measured by reduction in lung virus level of recipient mice, occurred if homologous viruses were used. Sharing of haemagglutinin specificity was shown to be important, but significant antiviral activity was still expressed if neither haemagglutinin nor neuraminidase antigenic specificities were shared. The antiviral effect was type-specific. Adoptive transfer of type A influenza immune T cells did not express antiviral activity against type B virus, and vice versa. On the basis of earlier work, the effector population in the transferred cells was cytotoxic T cells (Tc). Intranasal reinfection of mice with a heterologous type A virus sharing neither haemagglutinin nor neuraminidase antigenic specificity with the first infecting virus induced enhanced and earlier production of cross-reactive Tc against type A influenza viruses. This was paralleled by significantly lower virus levels in the lungs. The results of this work demonstrate heterotypic cell-mediated immunity in influenza virus infection in mice.

Animals↗
PubMed1978

Are cytotoxic T cells a common homeostatic mechanism in responses to viruses, homografts and tumours?

Cytotoxic T cells (Tc) have been shown to be important in the rejection of histoincompatible tissue grafts. They are also generated in mice during infection with viruses that are known to express viral coded antigens at the infected cell surface, although their presence is much easier to demonstrate with some viral infections than with others. Cell-mediated lysis only occurs if the Tc and virus-infected target cells share gene products coded for in the K or D region of the H-2 complex. In the case of both ectromelia and influenza virus infection of mice, transfer of specific Tc to histocompatible, infected mice has been shown to significantly lower the virus titre in target organs (spleen and lungs respectively). In experimental animals with some tumours, there is increasingly good evidence for the expression of tumour specific transplantation antigens (TSTA) in the membrane of the malignant cells, yet there is little evidence for the presence of specific Tc which might control the growth of the tumour. Possible reasons for the lack of generation or expression of Tc in these situations are discussed.

Animals↗
PubMed1977

Cytotoxic T cells specific for influenza virus-infected target cells.

Conditions are described for the generation and detection of murine cytotoxic cells which lyse influenza virus-infected target cells. A number of criteria indicated that most and probably all of the activity was due to T cells. These criteria included the susceptibity of cytotoxic activity to treatment with anti-theta ascitic fluid plus complement and the enhancement of lysis when there was H2 compatibility between donors of effector and virus-infected target cells.

Animals↗