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Biomedical subjects

P C Doherty

Publications and source records attributed to P C Doherty.

At least 253 records · Page 14Linked to original sources
PubMed1978

T-cell populations specifically depleted of alloreactive potential cannot be induced to lyse H-2-different virus-infected target cells.

Mouse lymphocyte populations of one parental H-2 type (A) were specificially depleted of alloreactive potential by filtration through irradiated A X B F1 recipients, and thoracic duct cells were then stimulated with virus in an A X B F1 environment. Experiments using T cells that had previously been exposed to influenza virus in the context of A established that cross-priming for recognition of viral components expressed on H-2-different (B) target cells does not occur. Furthermore, immunologically naive T cells stimulated with vaccinia virus, subsequent to negative selection for reactivity to B, could not be shown to interact with virus-infected cells of type B. Either there is no significant T-cell repertoire for recognition of virus associated with an H-2 determinant not encountered during ontogeny, or such T cells are also alloreactive and are removed during filtration.

Animals↗
PubMed1978

Influenzal pneumonia: early appearance of cross-reactive T cells in lungs of mice primed with heterologous type A viruses.

Mice were first primed with a type A or a type B influenza virus and then challenged intranasally at least 1 month later with another type A virus. Potent cytotoxic T cell populations were found in lung, and effector T cell function was also demonstrated in blood, spleen and mediastinal lymph nodes. Lymphocytes isolated from all of these anatomical sites were active against target cells infected with the same, or with serologically different, type A influenza viruses. Also, prior exposure to another type A virus resulted in more rapid development of effector function than was seen in mice that had first been infected with B/Lee. Cytotoxic T cell populations generated in mice with influenza thus tend overall to be type-specific, and there is substantial localization of these effector lymphocytes in the pneumonic lung.

Animals↗
PubMed1977

The control of specificity of cytotoxic T lymphocytes by the major histocompatibility complex (AG-B) in rats and identification of a new alloantigen system showing no AG-B restriction.

The regulatory influence of the rat major histocompatibility complex (MHC) (Ag-B complex) on the specificity of cytotoxic T lymphocytes was investigated. It was shown that the effector cells were specific for the original Ag-B phenotype in rat systems in which the responder and stimulator cell populations were unquestionably MHC identical but expressed different minor alloantigens of viral antigens. However, combined in vivo immunization and restimulation in culture of lymphocytes from rat strains previously thought to be MHC compatible resulted in the generation of cytotoxic T lymphocytes which effectively lyse not only target cells from the specific stimulating strains but also, to varying degrees, target cells from third party strains regardless of their Ag-B haplotypes. Genetic analysis indicates that expression of these cytotoxic T-cell-defined ("CT") antigens, found on both T and B lymphocytes, detectable thus far only with cytotoxic lymphocytes, is controlled by a single locus which segregates in backcross populations with the rat MHC. Discrepancies between the nature of CT antigens of the rat Ag-B and I-region specificities of the mouse H-2 are discussed.

Animals↗
PubMed1977

Antibody to influenza virus matrix protein detects a common antigen on the surface of cells infected with type A influenza viruses.

Antisera to the type-specific internal influenza virus matrix (M) protein of a type A influenza virus were produced in goats. In the presence of complement, anti-M serum was cytotoxic for target cells which were infected with a variety of serologically distinct type A influenza viruses, but did not react with type B influenza virus-infected cells. Absorption experiments indicated that anti-M serum detected a common antigen(s) on the surface of type A-infected cells. This serological cross-reactivity parallels the cross-reactivity observed for the cytotoxic T-cell response to type A viruses.

Antibodies, Viral↗
PubMed1977

Induction of virus-specific modifications recognized by cytotoxic T cells is not altered by prior substitution of target cells with trinitrophenol.

Cytotoxic thymus-derived lymphocytes generated after interaction with trinitrophenyl (TNP)-substituted or virus-infected cells only lyse H-2 compatible target cells modified with the component used to immunize (TNP or virus). Prior saturation of TNP-reactive sites inhibits neither the infectivity of influenza A viruses, nor the capacity of infected cells to develop antigenic changes recognized by influenza-immune T cells. The two antigens are distinct entities on the cell membrane and do not obviously compete to form interactions with H-2 molecules.

Animals↗
PubMed1977

Suppression of cell-mediated immunity by street rabies virus.

Mice lethally infected with street rabies virus failed to develop cytotoxic T cells specific for rabies virus-infected target cells, whereas high levels of cell-mediated cytotoxicity (CMC) were generated after nonfatal infection with the attenuated high egg passage (HEP) or ERA rabies virus strains. Furthermore concurrent infection with street, but not with HEP, rabies virus suppresses development of a primary (but not a secondary) CMC response specific for influenza virus. No cross-reactivity is found between effector T-cell populations from mice immunized with HEP or with influenza virus. It thus appears that street rabies virus, which is not known to replicate in the cells of immune system, induces some general defect in the primary CMC lymphocyte response, though restimulation of memory T-cell populations is unimpaired and there is no defect in antibody formation. Development of fatal rabies may reflect the operation of this selective immunosuppressive mechanism.

Animals↗
PubMed1977

Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses.

Specificity of cytotoxic T-cell function was investigated for a range of different influenza viruses. T cells from mice immunized with A or B strain influenza viruses, or with vaccinia virus, showed reciprocal exclusion of cytotoxicity. Extensive cross-reactivity was, however, found for lymphocyte populations from mice infected with a variety of serologically distinct influenza A viruses, though serum antibodies did not cross-react when tested in a radioimmunoassay using comparable target cells as immunoadsorbents. This apparent lack of T-cell specificity was recognized for immune spleen cells generated after intraperitoneal inoculation of high titers of virus, and for mediastinal lymph node populations from mice with pneumonia due to infection with much less virus. The phenomenon could not be explained on the basis of exposure to the chicken host component, which is common to A and B strain viruses. However, not all of the virus-immune T-cell clones are cross-reactive. Competitive-inhibition experiments indicate that a considerable proportion of the lymphocyte response is restricted to the immunizing virus. Even so, the less specific component is significant. Also, exposure to one type A virus was found to prime for an enhanced cell-mediated immunity response after challenge with a second, serologically different A strain virus.

Animals↗
PubMed1977

In vitro evidence of cell-mediated immunity after exposure of mice to both live and inactivated rabies virus.

Mice exposed to live or beta-propiolactone-inactivated rabies virus generated a strong, specific cell-mediated cytotoxic response which was generally maximal 6 days after inoculation. Release of 51Cr was apparently a function of immune thymus-derived lymphocytes (T cells) because it was abrogated by prior incubation of spleen cells with anti-thymus antiserum and complement but was undiminished by passage of spleen cells through nylon-wool columns. Cytotoxicity was always maximal for interactions in which thymus-derived cells and targets shared H-2 genes but, unlike the situation found in other assays of this type, considerable lysis of allogeneic, virus-infected target cells may also occur. Perhaps the most significant finding from these experiments is that an inactivated virus has been shown to stimulate a potent cytotoxic thymus-derived cell response. Manipulation of this experimental model may allow analysis of the antigens required for stimulation of cell-mediated immunity. A more practical consequence may be the development of more rational protocols for postexposure vaccination against rabies. Prior treatment of mice with antirabies antibody severely depressed the generation of cell-mediated immunity.

Animals↗
PubMed1977

Heterogeneity of the cytotoxic response of thymus-derived lymphocytes after immunization with influenza viruses.

Immunization of mice with serologically distinct type A influenza viruses results in development of highly crossreactive populations of cytotoxic thymus-derived lymphocytes (T cells). This can be shown both at the level of effector function and of priming for an enhanced response after challenge with another type A virus. Cytotoxic activity is demonstrable, in both the primary and secondary situations, only for H-2 compatible interactions. Further analysis by competitive inhibition experiments indicates that some of the T cell clones generated are specific for the virus used to immunize, while others are much less restricted. Secondary stimulation may result in preferential stimulation of the crossreactive T cells if the type A viruses used are very different serologically. When more closely related viruses are used, however, some degree of specificity is seen for the challenge virus. Even so, the patterns of crossreactivity observed are complex, and cannot be readily predicted on the basis of known serological relationships between surface hemagglutinin and neuraminidase antigens of type A influenza viruses.

Animals↗
PubMed1977

Diminished T cell surveillance function in old mice infected with lymphocyte choriomeningitis virus.

The cell-mediated immune response resulting from infection with lymphocytic choriomeningitis virus (LCMV) was compared in old (18--20 month) and young (4--6 month) random-bred ICR mice. Three separate assay systems were used: the level of virus-specific cytotoxic T-cell activity measured in vitro, time of onset of fatal cell-mediated immunopathology in vivo and adoptive transfer of inflammatory process to immunosuppressed, virus-infected recipients. The capacity of old mice to generate virus-immune effector T cells was, by all of these criteria, greatly diminished. It is suggested that the LCMV-specific T-cell response may prove a useful standard system for determining integrity of immunological surveillance function.

Age Factors↗
PubMed1976

H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. Evaluation of the role of H-2I region and non-H-2 genes in regulating immune response.

Lymphocytic choriomeningitis virus (LCMV) and ectromelia virus-specific T-cell-mediated cytotoxicity was assayed in various strain combinations using as targets peritoneal macrophages which have been shown to express Ia antigens. Virus-specific cytotoxicity was found only in H-2K- or D-region compatible combinations. I-region compatibility was not necessary nor alone sufficient for lysis. Six different I-region specificities had no obvious effect on the capacity to generate in vivo specific cytotoxicity (expressed in vitro) associated with Dd. Low LCMV-specific cytotoxic activity generated in DBA/2 mice was caused by the non-H-2 genetic background. This trait was inversely related to the infectious virus dose and recessive. Non-H-2 genes, possibly involved in controlling initial spread and multiplication of virus, seem to be, at least in the examples tested, more important in determining virus-specific cytotoxic T-cell activity in spleens than are Ir genes coded in H-2.

Animals↗
PubMed1976

The responses of the popliteal lymph node of the sheep to Ross River and Kunjin viruses.

The responses of popliteal lymph nodes of sheep to Ross River virus (RRV) or Kunjin virus (KV) have been studied by monitoring the cell populations, virus titre, antibody titre and plaque-forming cell (PFC) content of the efferent lymph. In a typical primary response to subcutaneous inoculation in the lower hind limb of either RRV or KV, the flow rate of lymph increased slightly. Increased cell concentrations in the lymph following inoculation caused the hourly cell outputs to rise 5.3- to 10.1-fold above pre-challenge levels. High cell outputs were sustained at greater than 3-fold above pre-challenge figures for up to 10 days. The increased number of large, blastic lymphocytes ranged from 4.0- to 14.9-fold; the increase in these cells usually followed the rise in total number of lymphocytes by 24 to 48 h and remained at greater than 3-fold higher levels for up to 12 days. Ross River virus was recovered in the efferent lymph for at least 36 h after inoculation. Sudden disappearance of the virus from the lymph was correlated with the onset of significant haemagglutination-inhibition antibody titres by 3 to 4 days after infection. In the efferent lymph, PFC were detected 5 to 7 days after primary or secondary inoculation of KV or RRV when lymphocytes were incubated with specific haemagglutinin-coated goose erythrocytes and guinea-pig complement. Antibody levels in the lymph were persistent while the occurrence of PFC was transient.

Animals↗