Vβ gene repertoires in T cells expanded in local self‐healing and lethal systemic murine cutaneous leishmaniasis

Lohoff, Michael; Steinert, Meike; Weiss, Angela; Röllinghoff, Martin; Balderas, Robert; Theofilopoulos, Argyrios N.

doi:10.1002/eji.1830240236

Cited by 4 publications

(2 citation statements)

References 20 publications

(11 reference statements)

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“…A similar pattern of Vβ chain expression was observed with CD4 + splenocytes from noninfected syngeneic mice, indicating that the distribution of TCR Vβ chains is not altered upon toxoplasma infection. Corresponding results have been reported in the leishmania system [11], suggesting that a broad variety of αβ T cells react with the pathogen. In vitro, T. gondii induces a selective expansion of non-immune CD8 + Vβ5 + T lymphocytes, implicating the action of a parasite superantigen [4].…”

Section: Discussionsupporting

confidence: 52%

T cell receptor specificities of Toxoplasma gondii-reactive mouse CD4 + T lymphocytes and Th1 clones

Reichmann

Długońska²,

Fischer³

1997

Medical Microbiology and Immunology

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The Toxoplasma gondii-directed CD4+ T cell response in chronically infected mice was studied with respect to both T cell receptor diversity and antigen specificities. T cell receptor chains V beta 4, 6, 8, 10, and 14 were predominantly found on toxoplasma-reactive CD4+ splenocytes. This repertoire was also detected among T. gondii-specific CD4+ T cell clones. Analysis of clonotypic cytokine profiles revealed typical Th1 clones secreting interleukin-2, interferon-gamma and tumour necrosis factor activity and Th2 clones producing interleukin-4 and interleukin-10. Five distinct toxoplasma antigens (p26, p40, p55, p58 and p60) were detected in electrophoretically separated toxoplasma lysate by five individual Th1 clones. Parallel testing of CD4+ T lymphocytes from infected mice confirmed that these specificities constitute the peak immunogenic fractions of toxoplasma lysate. The expression patterns of two clonotypic, T cell-stimulatory parasite antigens were studied in detail. While p55 was expressed by mouse-virulent and avirulent T. gondii isolates and in both the tachyzoite and bradyzoite stages, p58 was detected only in virulent strains from intraspecies subgroup I. Thus, we describe the heterogeneity of toxoplasmic immunodominant T cell antigens including a 58-kDa group I-restricted molecule which may provide a marker for virulent isolates.

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Section: Discussionsupporting

confidence: 52%

T cell receptor specificities of Toxoplasma gondii-reactive mouse CD4 + T lymphocytes and Th1 clones

Reichmann

Długońska²,

Fischer³

1997

Medical Microbiology and Immunology

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“…The following Th1 cell lines and clones were used: B10BI and F3.1, specific for bovine insulin, LNC-2 specific for Mycobacterium tuberculosis purified protein derivative (PPD) and C57/4 specific for LmAg, a Leishmania major antigen preparation (9)(10)(11)(12). Th2 cell lines and clones used were D10G4.1 specific for ovalbumin, BEL-16 and L1/1 specific for LmAg, and LNC-4 specific for PPD (10)(11)(12)(13)(14). The in vitro propagation of these T cells has been described (9).…”

Section: Methodsmentioning

confidence: 99%

A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo.

Lohoff¹,

Prechtl²,

Sommer³

et al. 1998

J. Clin. Invest.

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A transmembrane pump for organic anions was identified in resting murine T helper (Th) 2, but not Th1 lymphocyte cell clones, as revealed by extrusion of a fluorescent dye. Dye extrusion inhibition studies suggested that the pump may be the multidrug-resistance protein (MRP). The different expression of the pump in resting Th1 and Th2 cell clones correlated with their respective levels of MRP mRNA. The pump was inducible in Th1 cells by antigenic stimulation in vitro leading to equal expression in activated Th1 and Th2 cell clones. This suggested that dye extrusion might allow the detection of Th2 (resting or activated) or of activated Th1 cells ex vivo based on a functional parameter. To test this, mice were infected with Leishmania major parasites to activate L. major-specific T cells of either Th1 (C57BL/6 mice) or Th2 (BALB/c mice) phenotype: 2-3% of CD4+ lymph node T cells of both strains of mice extruded the dye, defining a cell subset that did not coincide with subsets defined by other activation markers. Fluorescence-activated cell-sorting revealed that the lymphokine response (Th1 or Th2, respectively) to L. major antigens was restricted to this dye-extruding subset.

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Selective Activation and Expansion of High-Affinity CD4+ T Cells in Resistant Mice upon Infection with Leishmania major

et al. 2000

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Using multimers of MHC class II molecules linked to a peptide derived from the Leishmania LACK antigen, we have compared the fate of parasite-specific CD4+ T cells in resistant and susceptible mice transgenic for the beta chain of a LACK-specific TCR. Activated T cells were readily detected in the draining lymph nodes of infected animals. Although the kinetics of activation and expansion were similar in both strains, T cells from susceptible and resistant mice expressed low- and high-affinity TCR, respectively. As T cells from resistant mice produced more IFN-gamma and less IL-4 than those from susceptible animals, our results suggest that differences in TCR usage between MHC-matched animals may influence the development of the antiparasite immune response.

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Vβ gene repertoires in T cells expanded in local self‐healing and lethal systemic murine cutaneous leishmaniasis

Cited by 4 publications

References 20 publications

T cell receptor specificities of Toxoplasma gondii-reactive mouse CD4 + T lymphocytes and Th1 clones

T cell receptor specificities of Toxoplasma gondii-reactive mouse CD4 + T lymphocytes and Th1 clones

A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo.

Selective Activation and Expansion of High-Affinity CD4+ T Cells in Resistant Mice upon Infection with Leishmania major

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