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BACKGROUND: Alloreactive T-cell responses are known to result in the production of large amounts of proinflammatory cytokines capable of activating and maturing dendritic cells (DC). However, it is unclear whether these allogeneic responses could also act as an adjuvant for concurrent antigen-specific responses. OBJECTIVE: To examine effects of simultaneous alloreactive and antigen-specific T-cell responses induced by semi-allogeneic DC. METHODS: Semi-allogeneic DC were generated from the F(1) progeny of inbred strains of mice (C57BL/6 and C3H, or C57BL/6 and DBA). We directly primed antigen-specific CD8(+) and CD4(+) T-cells from OT-I and OT-II mice, respectively, in the absence of allogeneic responses, in vitro, and in the presence or absence of alloreactivity in vivo. RESULTS: In vitro, semi-allogeneic DC cross-presented ovalbumin (OVA) to naïve CD8(+) OT-I transgenic T-cells, primed naïve CD4(+) OT-II transgenic T-cells and could stimulate strong alloreactive T-cell proliferation in a primary mixed lymphocyte reaction (MLR). In vivo, semi-allogeneic DC migrated efficiently to regional lymph nodes but did not survive there as long as autologous DC. In addition, they were not able to induce cytotoxic T-lymphocyte (CTL) activity to a target peptide, and only weakly stimulated adoptively transferred OT-II cells. The CD4(+) response was unchanged in allo-tolerized mice, indicating that alloreactive T-cell responses could not provide help for concurrently activated antigen-specific responses. In an EL4 tumour-treatment model, vaccination with semi-allogeneic DC/EL4 fusion hybrids, but not allogeneic DC/EL4 hybrids, significantly increased mouse survival. CONCLUSION: Expression of self-Major histocompatibility complex (MHC) by semi-allogeneic DC can cause the induction of antigen-specific immunity, however, concurrently activated allogeneic bystander responses do not provide helper or adjuvant effects.

Original publication

DOI

10.1007/s00262-007-0328-x

Type

Journal article

Journal

Cancer immunology, immunotherapy : CII

Publication Date

12/2007

Volume

56

Pages

1861 - 1873

Addresses

Department of Haematological and Molecular Medicine, King's College London, The Rayne Institute, London, SE5 9NU, UK.

Keywords

Dendritic Cells, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Animals, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Mice, Neoplasms, Inflammation, Cytokines, Immunotherapy, Lymphocyte Activation, Cell Movement, Binding, Competitive