Role of gamma/delta T cells in Vaccine Induced Immunity

Summary

Principal Investigator: DANIEL HOFT
Affiliation: Saint Louis University
Country: USA
Abstract: A subset of human T cells express T cell receptors (TCR) composed of gamma and delta subunits, homologous to alpha and beta proteins but encoded by distinct gene segments. The rapid response of gamma/delta T cells to microbial epithelial invasion suggests they represent a first line of defense for innate immunity. Others have shown that gamma/delta T cells provide a link between innate and adaptive immunity, producing cytokines such as IFN-gamma important for inducing type 1 immunity. We have identified a more direct adaptive immune role for gamma/delta T cells. We found that BCG vaccination induces human gamma/delta memory T cells characterized by more rapid and potent secondary responses. Vaccination with canarypox vectors and vaccinia also induced human gamma/delta memory T cell responses. The major focus of this RO1 has been to determine whether these memory gamma/delta T cell responses provide important helper and/or effector functions involved in protective immunity, and we have produced evidence for both. This competing continuation application will further investigate the following 3 hypotheses: #1) Mycobacteria- and poxviral-specific gamma/delta T cells have unique antigen specificities and can be used as bioindicators to identify pathogen derived stimulatory antigens, #2) Human gamma/delta T cells specific for mycobacterial and poxviral antigens can provide helper functions for the development of optimal memory immune alpha/beta T cell responses, and #3) Human gamma/delta T cells specific for mycobacteria and poxviruses can provide direct effector functions capable of inhibiting the replication of these intracellular pathogens. Studies of smallpox-specific gamma/delta T cell immunity, detailed TCR spectratyping comparisons between gamma/delta T cells induced by these different pathogens/vectors, identification of the pathogenic-specific antigenic molecules inducing these responses, and detailed studies of the mechanisms involved in gamma/delta T cell helper and effector immune functions are major additions in this application cycle. In addition, Aims 2 & 3 will specifically address in detail the antigen specificity of gamma/delta T cell responses. Another major addition is the inclusion of a subcontract to Dr. Dobos at Colorado State, who will pursue detailed biochemical studies designed to identify the specific components of mycobacteria and vaccinia that induce gamma/delta T cells relevant for vaccine development.
Funding Period: 2000-07-01 - 2012-02-28
more information: NIH RePORT

Top Publications

  1. ncbi Flow-cytometric detection of vaccinia-induced memory effector CD4(+), CD8(+), and gamma delta TCR(+) T cells capable of antigen-specific expansion and effector functions
    Getahun Abate
    Department of Internal Medicine, Saint Louis University, St. Louis, Missouri 63110, USA
    J Infect Dis 192:1362-71. 2005
  2. ncbi Enhancement of innate and cell-mediated immunity by antimycobacterial antibodies
    S de Valliere
    Department of Internal Medicine, Saint Louis University Health Science Center, MO 63110, USA
    Infect Immun 73:6711-20. 2005
  3. ncbi Only a subset of phosphoantigen-responsive gamma9delta2 T cells mediate protective tuberculosis immunity
    Charles T Spencer
    Department of Internal Medicine, Saint Louis University, St Louis, MO 63104, USA
    J Immunol 181:4471-84. 2008
  4. ncbi A new recombinant bacille Calmette-Guérin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers
    Daniel F Hoft
    Department of Internal Medicine and Molecular Biology, Saint Louis University Medical Center, and Center for Vaccine Development, Saint Louis, MO 63104, USA
    J Infect Dis 198:1491-501. 2008

Scientific Experts

  • DANIEL HOFT
  • Getahun Abate
  • Charles T Spencer
  • S de Valliere
  • Azra Blazevic
  • Joy Eslick
  • A Blazevic
  • Thomas P Monath
  • Frances K Newman
  • Robert B Belshe
  • Sharon E Frey
  • G Abate
  • R M Heuertz

Detail Information

Publications5

  1. ncbi Flow-cytometric detection of vaccinia-induced memory effector CD4(+), CD8(+), and gamma delta TCR(+) T cells capable of antigen-specific expansion and effector functions
    Getahun Abate
    Department of Internal Medicine, Saint Louis University, St. Louis, Missouri 63110, USA
    J Infect Dis 192:1362-71. 2005
    ..CFSE-based flow-cytometric assays will be useful in evaluating cell-mediated immune responses induced by new smallpox vaccines...
  2. ncbi Enhancement of innate and cell-mediated immunity by antimycobacterial antibodies
    S de Valliere
    Department of Internal Medicine, Saint Louis University Health Science Center, MO 63110, USA
    Infect Immun 73:6711-20. 2005
    ..We conclude that mycobacterium-specific antibodies are capable of enhancing both innate and cell-mediated immune responses to mycobacteria...
  3. ncbi Only a subset of phosphoantigen-responsive gamma9delta2 T cells mediate protective tuberculosis immunity
    Charles T Spencer
    Department of Internal Medicine, Saint Louis University, St Louis, MO 63104, USA
    J Immunol 181:4471-84. 2008
    ..Specific targeting of protective gamma(9)delta(2) T cell subsets will be important for future tuberculosis vaccines...
  4. ncbi A new recombinant bacille Calmette-Guérin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers
    Daniel F Hoft
    Department of Internal Medicine and Molecular Biology, Saint Louis University Medical Center, and Center for Vaccine Development, Saint Louis, MO 63104, USA
    J Infect Dis 198:1491-501. 2008
    ..rBCG30, which overexpresses the Mycobacterium tuberculosis secreted antigen Ag85b, was the first rBCG shown to induce significantly greater protection against TB in animals than parental BCG...