Ocular immunology and inflammation · 2000
In-vivo impaired T helper 1 cell development in submandibular lymph nodes due to IL-12 deficiency following antigen injection into the anterior chamber of the eye.
СтатьяПоддержка исследования: вне правительства СШАПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Perez V L, Biuckians A J, Streilein J W
Аннотация
PURPOSE: To determine the functional properties of antigen-specific T cells that accumulate in lymph nodes following injection of antigen into the anterior chamber (AC).
METHODS: Ovalbumin (OVA)-specific, CD4(+) transgenic T cell receptor (Tcr) T cells (KJ-126(+)) from DO11.10 mice were adoptively transferred into unirradiated syngeneic BALB/c mice who then received an injection of OVA in the AC or subcutaneously (SC). Three days later, KJ126(+) T cells in draining and non-draining lymph nodes were analyzed for clonal expansion, activation, and cell-cycle status by flow cytometry. In addition, the cells' functional phenotype was assessed in vitro by proliferation assays and cytokine production by ELISA.
RESULTS: Tcr T cells localized exclusively to draining lymph nodes after injection of OVA into the AC (neck) and SC (neck, axilla, brachial). In both cases, the KJ126(+) T cells displayed evidence of in-vivo activation and proliferation. T cells from AC-injected donors when stimulated in vitro with OVA produced small amounts of IL-2, but no IFN-gamma, IL-4, IL-5, IL-10, or TGFbeta. By contrast, T cells from SC-injected animals displayed a Th1-like phenotype (IL-2, IFN-gamma). The draining lymph nodes of mice that received systemic or intraocular administration of exogenous IL-12 at the time of the AC injection of OVA also contained KJ126(+) T cells that secreted IFN-gamma and IL-2.
CONCLUSION: Antigen attracts antigen-specific T cells to lymph nodes that drain the injection site. Whereas responding T cells in nodes draining SC-injection sites differentiated into Th1-like cells, T cells in nodes draining AC injection failed to differentiated beyond the capacity to secrete IL-2 in response to antigen. Since the failure was reversed by exogenous IL-12, we propose that orderly differentiation of antigen-specific T cells down the Th1 pathway is aborted by the eye, because of a deficit in IL-12 production.
METHODS: Ovalbumin (OVA)-specific, CD4(+) transgenic T cell receptor (Tcr) T cells (KJ-126(+)) from DO11.10 mice were adoptively transferred into unirradiated syngeneic BALB/c mice who then received an injection of OVA in the AC or subcutaneously (SC). Three days later, KJ126(+) T cells in draining and non-draining lymph nodes were analyzed for clonal expansion, activation, and cell-cycle status by flow cytometry. In addition, the cells' functional phenotype was assessed in vitro by proliferation assays and cytokine production by ELISA.
RESULTS: Tcr T cells localized exclusively to draining lymph nodes after injection of OVA into the AC (neck) and SC (neck, axilla, brachial). In both cases, the KJ126(+) T cells displayed evidence of in-vivo activation and proliferation. T cells from AC-injected donors when stimulated in vitro with OVA produced small amounts of IL-2, but no IFN-gamma, IL-4, IL-5, IL-10, or TGFbeta. By contrast, T cells from SC-injected animals displayed a Th1-like phenotype (IL-2, IFN-gamma). The draining lymph nodes of mice that received systemic or intraocular administration of exogenous IL-12 at the time of the AC injection of OVA also contained KJ126(+) T cells that secreted IFN-gamma and IL-2.
CONCLUSION: Antigen attracts antigen-specific T cells to lymph nodes that drain the injection site. Whereas responding T cells in nodes draining SC-injection sites differentiated into Th1-like cells, T cells in nodes draining AC injection failed to differentiated beyond the capacity to secrete IL-2 in response to antigen. Since the failure was reversed by exogenous IL-12, we propose that orderly differentiation of antigen-specific T cells down the Th1 pathway is aborted by the eye, because of a deficit in IL-12 production.