Cancer Immunol Immunother
December 2012
Mast cells have emerged as critical intermediaries in the regulation of peripheral tolerance. Their presence in many precancerous lesions and tumors is associated with a poor prognosis, suggesting mast cells may promote an immunosuppressive tumor microenvironment and impede the development of protective anti-tumor immunity. The studies presented herein investigate how mast cells influence tumor-specific T cell responses.
View Article and Find Full Text PDFThe tumor microenvironment (TME), which is composed of stromal cells such as endothelial cells, fibroblasts, and immune cells, provides a supportive niche promoting the growth and invasion of tumors. The TME also raises an immunosuppressive barrier to effective antitumor immune responses and is therefore emerging as a target for cancer immunotherapies. Mast cells (MCs) accumulate in the TME at early stages, and their presence in the TME is associated with poor prognosis in many aggressive human cancers.
View Article and Find Full Text PDFCFA is a strong adjuvant capable of stimulating cellular immune responses. Paradoxically, adjuvant immunotherapy by prior exposure to CFA or live mycobacteria suppresses the severity of experimental autoimmune encephalomyelitis (EAE) and spontaneous diabetes in rodents. In this study, we investigated immune responses during adjuvant immunotherapy of EAE.
View Article and Find Full Text PDFDespite many studies, the regulation of CD4(+) T cell apoptosis during the shutdown of immune responses is not fully understood. We have investigated the molecular mechanisms of IFN-gamma in regulating apoptosis of CD4(+) T cells during bacillus Calmette-Guérin (BCG) infection of mice. Our data provide new insight into the regulation of CD4(+) T cell apoptosis by IFN-gamma.
View Article and Find Full Text PDFInfection with Mycobacterium bovis Bacille Calmette Guérin (BCG) induces high levels of apoptosis among activated CD4+ T cells. We have investigated the specificity of this pro-apoptotic response and its influence on CD4+ T cell mediated autoimmunity. Apoptosis induced by BCG-infection is unrelated to antigenic specificity, as demonstrated by the increased apoptosis of activated TCR transgenic CD4+ T cells of unrelated specificity.
View Article and Find Full Text PDFExperimental autoimmune encephalomyelitis (EAE) disease was accelerated iNOS-deficient (KO) mice: coinciding with greatly increased numbers of Ag-specific Th1 cells in the periphery that appeared to rapidly shift from the spleen to the CNS during onset of disease symptoms. iNOS KO mice had significantly increased Th1 cells in the CNS versus wild-type mice. Apoptosis of CNS-infiltrating CD4(+) T cells was impaired in iNOS KO mice at peak of disease; consequently, these mice had more CNS-infiltrating CD4(+) T cells.
View Article and Find Full Text PDFGranulomatous disease following exposure to Mycobacterium tuberculosis, Mycobacterium leprae or Mycobacterium avium is correlated with strong inflammatory and protective responses. The mouse model of mycobacterial infection provides an excellent tool with which to examine the inter-relationship between protective cell-mediated immunity and tissue-damaging hypersensitivity. It is well established that T cells and interferon (IFN)-gamma are necessary components of anti-bacterial protection.
View Article and Find Full Text PDF