Use of adoptive transfer of T‐cell antigen‐receptor‐transgenic T cells for the study of T‐cell activation in vivo

Pape, Kathryn A.; Kearney, Elizabeth R.; Khoruts, Alexander; Mondino, Anna; Merica, Rebecca; Chen, Zong Ming; Ingulli, Elizabeth; White, J. C.; Johnson, Jennifer J.; Jenkins, Marc K.

doi:10.1111/j.1600-065x.1997.tb00959.x

Cited by 191 publications

(153 citation statements)

References 60 publications

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“…In fact, our observation that TS1 hosts reject MHC disparate allografts in 10 days compared with an average of 28 days for HA104 graft rejection was unexpected in light of the fact that the precursor frequency of T cells reactive for the allogeneic donor is likely to be many fold lower than the frequency of HA-specific T cells in TS1 recipients. Although differences in Ag density (HA vs Allo-MHC) on the graft could contribute to this result, an alternate hypothesis is that rejection of HA grafts by TS1 hosts is impeded by too high a frequency of responding T cells (43). In support of the latter possibility is our finding that HA104 graft rejection is typically more rapid following transfer of a small number of TS1 T cells to BALB/c hosts than in naive TS1 recipients.…”

Section: Discussionsupporting

confidence: 75%

CD25+ Immunoregulatory CD4 T Cells Mediate Acquired Central Transplantation Tolerance

Trani

Moore

Jarrett

et al. 2003

The Journal of Immunology

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Transplantation tolerance is induced reliably in experimental animals following intrathymic inoculation with the relevant donor strain Ags; however, the immunological mechanisms responsible for the induction and maintenance of the tolerant state remain unknown. We investigated these mechanisms using TCR transgenic mice (TS1) that carry T cells specific for an immunodominant, MHC class II-restricted peptide (S1) of the influenza PR8 hemagglutinin (HA) molecule. We demonstrated that TS1 mice reject skin grafts that have transgene-encoded HA molecules (HA104) as their sole antigenic disparity and that intrathymic but not i.v. inoculation of TS1 mice with S1 peptide induces tolerance to HA-expressing skin grafts. Intrathymic peptide inoculation was associated with a dose-dependent reduction in T cells bearing high levels of TCR specific for HA. However, this reduction was both incomplete and transient, with a full recovery of S1-specific thymocytes by 4 wk. Peptide inoculation into the thymus also resulted in the generation of immunoregulatory T cells (CD4+CD25+) that migrated to the peripheral lymphoid organs. Adoptive transfer experiments using FACS sorted CD4+CD25− and CD4+CD25+ T cells from tolerant mice revealed that the former but not the latter maintain the capacity to induce rejection of HA bearing skin allografts in syngeneic hosts. Our results suggest that both clonal frequency reduction in the thymus and immunoregulatory T cells exported from the thymus are critical to transplantation tolerance induced by intrathymic Ag inoculation.

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Section: Discussionsupporting

confidence: 75%

CD25+ Immunoregulatory CD4 T Cells Mediate Acquired Central Transplantation Tolerance

Trani

Moore

Jarrett

et al. 2003

The Journal of Immunology

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“…injection) of OVA or OVA 323-339 in this T cell transfer model induced a rapid, strong, transient DO11.10 T cell proliferation, resulting in a state of nonresponsiveness of these T cells upon subsequent challenge in vivo or in vitro. Moreover, they described that the induction of a more local and less transient response, by s.c. administration of OVA 323-339 in CFA, resulted in a significantly enhanced T cell response upon in vitro stimulation with OVA 323-339 (19,24). Previously, we described that successful immunotherapy was associated with decreased Th2 responses (9, 10).…”

Section: Discussionmentioning

confidence: 93%

The Efficacy of Immunotherapy in an Experimental Murine Model of Allergic Asthma Is Related to the Strength and Site of T Cell Activation During Immunotherapy

Janssen

Oosterhout

Nijkamp

et al. 2000

The Journal of Immunology

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In the present study, the relation between the efficacy of immunotherapy, and the strength and site of T cell activation during immunotherapy was evaluated. We used a model of allergic asthma in which OVA-sensitized and OVA-challenged mice display increased airway hyperresponsiveness, airway inflammation, and Th2 cytokine production by OVA-specific T cells. In this model, different immunotherapy strategies, including different routes of administration, or treatment with entire OVA or the immunodominant T cell epitope OVA323–339, or treatment with a peptide analogue of OVA323–339 with altered T cell activation capacity were studied. To gain more insight in how immunotherapy affects allergen-specific T cells, the site of Ag-specific T cell activation and the magnitude of the T cell response induced during different immunotherapy strategies were determined using an adoptive transfer model. Our data suggest that amelioration of airway hyperresponsiveness and inflammation is associated with the induction of a strong, synchronized, and systemic T cell response, resulting in a decreased OVA-specific Th2 response. In contrast, deterioration of the disease after immunotherapy is associated with the induction of a weak nonsynchronized T cell response, resulting in the enhancement of the OVA-specific Th2 response after challenge.

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“…A commonly used alternative to visualize Th cell responses in mice is the adoptive transfer of traceable populations of TCR-transgenic T cells into congenic mice [25]. This method is especially important to allow tracking of early differentiation events of naive T cells, which are too few in number to be followed in a nonmanipulated immune system.…”

Section: Discussionmentioning

confidence: 99%

Identification and isolation of murine antigen‐reactive T cells according to CD154 expression

et al. 2007

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T helper (Th) cells are central regulators of adaptive immune responses. However, the detection of the small number of Th cells specific for a particular antigen or pathogen is still a major challenge. CD154 was recently introduced as a marker for antigen-specific Th cells. To date, this technology was not applicable for mice -arguably the most important immunological model system. CD154 is difficult to detect due to its rapid removal from the cell surface upon binding to CD40 during antigen-specific activation by APC. We present an efficient strategy to block the degradation of murine CD154 by combined use of antibodies against CD40 and CD154. This strategy makes CD154 easily accessible for surface staining, which allows isolation and expansion of rare antigen specific T cells. Importantly, CD154 identified all specific T cells in strongly Th1-or Th2-polarized immune responses against pathogens like Salmonella typhimurium and Heligmosomoides polygyrus, independent of their potential to produce cytokines. We demonstrate that CD154 can in fact be used as a reliable marker for antigen-specific CD4 T cells in mice, offering a unique option to analyze, isolate and rapidly expand the entire pool of Th-cells generated during a physiological T cell response in vivo.

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Use of adoptive transfer of T‐cell antigen‐receptor‐transgenic T cells for the study of T‐cell activation in vivo

Cited by 191 publications

References 60 publications

CD25+ Immunoregulatory CD4 T Cells Mediate Acquired Central Transplantation Tolerance

CD25+ Immunoregulatory CD4 T Cells Mediate Acquired Central Transplantation Tolerance

The Efficacy of Immunotherapy in an Experimental Murine Model of Allergic Asthma Is Related to the Strength and Site of T Cell Activation During Immunotherapy

Identification and isolation of murine antigen‐reactive T cells according to CD154 expression

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