Effect of Murine Strain and Viral Strain on the Pathogenesis of Lymphocytic Choriomeningitis Infection and a Study of Footpad Responses

Tosolini, F. A.; Mims, Cedric

doi:10.1093/infdis/123.2.134

Cited by 68 publications

(45 citation statements)

References 16 publications

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“…In case of tetramer staining, cells were incubated with H-2D b /gp [33][34][35][36][37][38][39][40][41] tetramer for 1 h at 20°C before surface labeling. To detect intracellular IFN-␥, splenocytes (10 7 /ml) were incubated with an immunodominant MHC-class I-restricted epitope (LCMV gp [33][34][35][36][37][38][39][40][41] , 0.1 g/ml), monensin (3 M), and IL-2 (50 IU/ml) for 5 h, after which cells were surface labeled, fixed, and permeabilized using PBS/saponin (0.05%), and anti-IFN-␥ was added. After incubation for 20 min in the dark, cells were washed twice in PBS/saponin.…”

Section: Fluorescence Staining and Flow Cytometric Analysismentioning

confidence: 99%

“…To examine the functional role of ␣ 1 ␤ 1 and ␣ 2 ␤ 1 on T cells, LCMV-induced T cell-mediated inflammation in a collagen-rich environment, the footpad, was studied (38). This is a primarily CD8 ϩ T cell-mediated inflammatory reaction generated in response to virus replicating locally in the footpad (25,31,36).…”

Section: Functional Role Of ␣ 1 ␤ 1 and ␣ 2 ␤ 1 On Virus-specific Cd8mentioning

confidence: 99%

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Expression and Functional Importance of Collagen-Binding Integrins, α1β1 and α2β1, on Virus-Activated T Cells

Andreasen¹,

Thomsen²,

Koteliansky

et al. 2003

The Journal of Immunology

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Adhesive interactions are crucial to cell migration into inflammatory sites. Using murine lymphocytic choriomeningitis virus as an Ag model system, we have investigated expression and function of collagen-binding integrins, α1β1 and α2β1, on activated and memory T cells. Using this system and MHC tetramers to define Ag-specific T cells, we demonstrate that contrary to being VLAs, expression of α1β1 and α2β1 can be rapidly induced on acutely activated T cells, that expression of α1β1 remains elevated on memory T cells, and that expression of α1β1 parallels that of viral-specific effector CD8+ T cells (defined by tetramer and IFN-γ staining). In an adoptive transfer model, mAb-mediated blockade of these integrins on activated effector and memory T cells inhibited Ag-specific delayed-type hypersensitivity responses; similar decreased responses were seen upon transfer of α1-deficient activated/memory T cells. Thus, expression of α1β1 and α2β1 integrins on activated T cells is directly functionally important for generation of inflammatory responses within tissues. Finally, the inhibitory effect of α1β1 blockade on the delayed-type hypersensitivity response could be bypassed by direct injection of Ag-specific T cells to inflammatory sites, demonstrating for the first time in vivo that collagen-binding integrins are involved in leukocyte migration into tissues.

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Section: Fluorescence Staining and Flow Cytometric Analysismentioning

confidence: 99%

Section: Functional Role Of ␣ 1 ␤ 1 and ␣ 2 ␤ 1 On Virus-specific Cd8mentioning

confidence: 99%

Expression and Functional Importance of Collagen-Binding Integrins, α1β1 and α2β1, on Virus-Activated T Cells

Andreasen¹,

Thomsen²,

Koteliansky

et al. 2003

The Journal of Immunology

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“…Delayed-type hypersensitivity (DTH) may be considered as a model for T-cell-mediated inflammatory responses (10). The present investigations were designed to determine whether successful transfer of DTH by lymphoid cells from sensitized to naive mice might be restricted by genes of the MHC.…”

mentioning

confidence: 99%

H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice.

Miller¹,

Vadas²,

Whitelaw³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

152

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Sensitized lymphocytes can transfer a state of delayed-type hypersensitivity to soluble protein antigens to naive mice only if donor and recipient share the I-A region of the H-2 gene complex. Identity at the K or D region is not essential. The restriction is unlikely to result from ineffective homing of the injected cells or from their early destruction. It is thought to reflect a requirement for an Ir-gene controlled mechanism which governs effective interaction between sensitized T lymphocytes and antigen presented on the surface of macrophages.There is considerable evidence that T (thymus-derived) cell activities are regulated by genes in the major histocompatibility complex (MHC). Thus, in mice, histoincompatible T cells may not function as helpers for antibody-forming precursor B (bone-marrow-derived) cells in some transfer systems (1). In guinea pigs, maximal lymphocyte proliferation in response to antigen-pulsed macrophages occurs in vitro only when lymphocytes and macrophages have at least part of the MHC in common (2). Lysis of virus-infected or chemically modified target cells by cytotoxic T cells in mice is possible only when these cells share one H-2 haplotype (3, 4). Requirement for H-2 compatibility is also evident in vivo in immunopathology induced by T cells (5) and in T-cellmediated protection against bacterial infections (6). In the case of specific lysis of target cells, identity is essential at the K or D regions of the H-2 complex, not at the I region (4, 7). On the other hand, in order for cooperative interactions to occur between T and B lymphocytes in some antibody responses, identity is required at the I region, not at the K, D, or S regions (8). Likewise, optimal induction of helper T cells by macrophage-associated antigen was found to require identity at the I region of the MHC (9).Delayed-type hypersensitivity (DTH) may be considered as a model for T-cell-mediated inflammatory responses (10). The present investigations were designed to determine whether successful transfer of DTH by lymphoid cells from sensitized to naive mice might be restricted by genes of the MHC. These studies were made possible by the use of congenic strains of mice and of a new radioisotopic assay which gives an objective measure of the extent of DTH in mice (11,12).MATERIALS AND METHODS Mice. Female mice (2-3 month old) were used for sensitization. Mice of both sexes served as recipients of sensitized cells. Highly inbred specific pathogen-free CBA/CaHWehi, C57BL/6JWehi, and BALB/cAnBrWehi mice were transferred to conventional rooms for the duration of the experi- Sensitization. Two days before sensitization mice were given 200 mg/kg of cyclophosphamide (Endoxan-Asta) subcutaneously since this was found to allow maximal levels of sensitivity in mice (11). For sensitization to fowl (chicken) gamma globulin (FGG), the antigen was emulsified in complete Freund's adjuvant and 0.15 ml (containing 400 sg of FGG) was injected in three subcutaneous sites divided between the two hind footpads and abdomen. For s...

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“…inoculation, it is possible to determine the kinetics of the DTH response by measuring footpad swelling whose peak correlates with the peak of CTLs. [35][36][37] In this study, we determined whether a GCV treatment could control the immunopathology occurring after LCMV infection in mice expressing TK in their T cells. For this purpose, we used transgenic mice expressing the TK gene 38 under the transcriptional control of CD4-derived regulatory sequences driving in vivo expression in T cells.…”

Section: Introductionmentioning

confidence: 99%

Transient control of a virus-induced immunopathology by genetic immunosuppression

et al. 2000

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The ability to control T cell reactivity using suicide genes opens new perspectives for the treatment of T cell-mediated diseases. The therapeutic effect is achieved by the selective killing of thymidine kinase gene-modified activated T cells by ganciclovir (GCV). This strategy has been shown to control T cell alloreactivity efficiently after bone marrow or solid organ transplantation. Here, we aimed to determine whether an immunopathological process induced by a viral infection could be controlled by GCV when T cells express a thymidine kinase transgene. When transgenic mice were infected with the lymphocytic choriomeningitis virus, administration of GCV resulted in an efficient, but only transient, control of the immunopathological immune response. Further analysis

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Effect of Murine Strain and Viral Strain on the Pathogenesis of Lymphocytic Choriomeningitis Infection and a Study of Footpad Responses

Cited by 68 publications

References 16 publications

Expression and Functional Importance of Collagen-Binding Integrins, α1β1 and α2β1, on Virus-Activated T Cells

Expression and Functional Importance of Collagen-Binding Integrins, α1β1 and α2β1, on Virus-Activated T Cells

H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice.

Transient control of a virus-induced immunopathology by genetic immunosuppression

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