Aspergillus-specific CD4+ T cells in Invasive Aspergillosis

Summary

Principal Investigator: Amariliz Rivera
Abstract: Aspergillus fumigatus is a clinically important fungal pathogen that causes invasive disease in immunocompromised hosts. Leukemia patients receiving intense chemotherapy regimens and bone marrow transplanted patients are particularly at risk for Invasive Aspergillosis (IA) with an associated mortality rate of approximately 90%. Studies in mouse models of IA have suggested that Aspergillus-specific IFN-gamma secreting T lymphocytes play a protective role by limiting invasive fungal disease while IL-4 and IL-13 producing T cells have a deleterious impact. Although it is clear from these studies that CD4 T cells influence the outcome of A. fumigatus infection, many of the factors that determine T cell activation and recruitment remain poorly defined. Moreover, it remains to be determined whether Aspergillus-specific CD4 T cells can mediate the resolution of established disease. In order to begin to address these questions, the candidate, Dr. Amariliz Rivera, cloned CD4 T cells specific for A. fumigatus, isolated the genes encoding the antigen specific alpha and beta chains of the T cell receptor (TCR) and generated TCR transgenic mice. Preliminary results demonstrate that these mice express a functional TCR that recognizes A. fumigatus hyphae. The availability of monoclonal Aspergillus-specific CD4 T cells will give the candidate the unique opportunity to address the following aims: 1) to characterize the activation and differentiation of CD4 T cell responses to inhaled A. fumigatus spores, 2) to establish the role of the regulatory cytokines IL-10 and TGFbeta in this process, 3) to examine the influence of concurrent innate inflammatory responses on T cell activation and 4) to establish whether A. fumigatus-specific T cells can confer protection from IA. Furthermore, these studies will establish the foundation for the potential therapeutic use of CD4 T cells against fungal infections in the cancer patient. Dr. Rivera will perform these studies under the guidance of Dr. Eric G. Pamer at Memorial Sloan Kettering Cancer Center. Through this K01 award the candidate will gain the skills and experience necessary to successfully compete for an independent faculty position. As a woman of Puerto Rican descent the candidate will strive to be an outstanding role model for younger Hispanic scientists.
Funding Period: ----------------2006 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Innate immune activation and CD4+ T cell priming during respiratory fungal infection
    Amariliz Rivera
    Infectious Diseases Service, Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 9, New York, New York 10021, USA
    Immunity 25:665-75. 2006
  2. pmc Cytokines and the regulation of fungus-specific CD4 T cell differentiation
    Vanessa Espinosa
    Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 So Orange Avenue, MSB F601, Newark, NJ 07101, USA
    Cytokine 58:100-6. 2012
  3. pmc Aberrant tissue localization of fungus-specific CD4+ T cells in IL-10-deficient mice
    Amariliz Rivera
    Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Immunol 183:631-41. 2009
  4. pmc Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection
    Tobias M Hohl
    Infectious Disease Service, Department of Medicine, and Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell Host Microbe 6:470-81. 2009
  5. pmc Dectin-1 diversifies Aspergillus fumigatus-specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation
    Amariliz Rivera
    Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Exp Med 208:369-81. 2011

Scientific Experts

Detail Information

Publications5

  1. ncbi Innate immune activation and CD4+ T cell priming during respiratory fungal infection
    Amariliz Rivera
    Infectious Diseases Service, Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 9, New York, New York 10021, USA
    Immunity 25:665-75. 2006
    ....
  2. pmc Cytokines and the regulation of fungus-specific CD4 T cell differentiation
    Vanessa Espinosa
    Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 So Orange Avenue, MSB F601, Newark, NJ 07101, USA
    Cytokine 58:100-6. 2012
    ..We will also highlight the contributions of innate receptors involved in recognition of fungi and how they shape cytokine secretion and CD4 T cell differentiation...
  3. pmc Aberrant tissue localization of fungus-specific CD4+ T cells in IL-10-deficient mice
    Amariliz Rivera
    Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Immunol 183:631-41. 2009
    ..Our studies demonstrate that disregulated immune responses in the gut can result in dramatic redistribution of pathogen-specific T cells within the host...
  4. pmc Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection
    Tobias M Hohl
    Infectious Disease Service, Department of Medicine, and Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell Host Microbe 6:470-81. 2009
    ....
  5. pmc Dectin-1 diversifies Aspergillus fumigatus-specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation
    Amariliz Rivera
    Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Exp Med 208:369-81. 2011
    ..fumigatus-specific CD4 T cells and enabling Th17 differentiation...