Tuberculosis remains an important life-threatening disease and has recently been declared to be a global health emergency by the World Health Organization. While human CD4 T cells play a crucial role in immune protection against M. tuberculosis infection, other T cell populations are poorly characterized for their roles in immunity to tuberculosis. We have recently demonstrated that memory responses of mycobacterium-specific CDS T cells after M. tuberculosis infection coincided with protection against fatal tuberculosis in BCG-vaccinated monkeys, and that antibody-mediated depletion of CD8 T cells in monkeys with protective memory resulted in the development of severe forms of tuberculosis following M. tuberculosis re-infection by aerosol. Based on these results, we hypothesize that mycobacterium-specific CD8 T cells are an important component of immunity against tuberculosis. In testing this hypothesis, we will answer immune mechanistic questions involving CD8 T cell-mediated anti-tuberculosis immunity. We will: I. Determine the role of CD8 T cells in resistance to primary M. tuberculosis infection. II. Determine the role of CD8 T cells in adaptive immunity to M. tuberculosis re-infection and reactivation tuberculosis. A. Determine the role of CD8 T cells in adaptive immunity against M. tuberculosis re-infection. B. Determine the role of CD8 T cells in controlling reactivation tuberculosis in normal monkeys and SIVmac-infected macaques. III. Determine if vaccine-elicited CD8 T cell responses can confer some protection against tuberculosis in immune competent and SHIV-infected monkeys. A. Examine vaccine-elicited CD8 T cell responses and determine if such immune responses can confer some degree of protection against M. tuberculosis infection in normal monkeys. B. Determine if vaccine-elicited CD8 T cell responses can contribute to immune protection against tuberculosis in SHIV-89.6P-infected monkeys.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR013601-10
Application #
7477994
Study Section
AIDS-associated Opportunistic Infections and Cancer Study Section (AOIC)
Program Officer
O'Neill, Raymond R
Project Start
1998-06-01
Project End
2010-07-31
Budget Start
2008-08-01
Budget End
2010-07-31
Support Year
10
Fiscal Year
2008
Total Cost
$642,746
Indirect Cost
Name
University of Illinois at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Yang, Rui; Yang, Enzhuo; Shen, Ling et al. (2018) IL-12+IL-18 Cosignaling in Human Macrophages and Lung Epithelial Cells Activates Cathelicidin and Autophagy, Inhibiting Intracellular Mycobacterial Growth. J Immunol 200:2405-2417
Shen, Hongbo; Gu, Jin; Xiao, Heping et al. (2017) Selective Destruction of Interleukin 23-Induced Expansion of a Major Antigen-Specific ?? T-Cell Subset in Patients With Tuberculosis. J Infect Dis 215:420-430
Chen, Zheng W (2016) Protective immune responses of major V?2V?2 T-cell subset in M. tuberculosis infection. Curr Opin Immunol 42:105-112
Zhang, Jun-Ai; Liu, Gan-Bin; Zheng, Bi-Ying et al. (2016) Tuberculosis-sensitized monocytes sustain immune response of interleukin-37. Mol Immunol 79:14-21
Wang, Yang; Zhong, Huiling; Xie, Xiaodan et al. (2015) Long noncoding RNA derived from CD244 signaling epigenetically controls CD8+ T-cell immune responses in tuberculosis infection. Proc Natl Acad Sci U S A 112:E3883-92
Shen, Hongbo; Wang, Yunqi; Chen, Crystal Y et al. (2015) Th17-related cytokines contribute to recall-like expansion/effector function of HMBPP-specific V?2V?2 T cells after Mycobacterium tuberculosis infection or vaccination. Eur J Immunol 45:442-51
Frencher, James T; Shen, Hongbo; Yan, Lin et al. (2014) HMBPP-deficient Listeria mutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of V?2V?2 T cells. J Leukoc Biol 96:957-67
Yao, Shuyu; Huang, Dan; Chen, Crystal Y et al. (2014) CD4+ T cells contain early extrapulmonary tuberculosis (TB) dissemination and rapid TB progression and sustain multieffector functions of CD8+ T and CD3- lymphocytes: mechanisms of CD4+ T cell immunity. J Immunol 192:2120-32
Chen, Zheng W (2013) Multifunctional immune responses of HMBPP-specific V?2V?2 T cells in M. tuberculosis and other infections. Cell Mol Immunol 10:58-64
Chen, Crystal Y; Yao, Shuyu; Huang, Dan et al. (2013) Phosphoantigen/IL2 expansion and differentiation of V?2V?2 T cells increase resistance to tuberculosis in nonhuman primates. PLoS Pathog 9:e1003501

Showing the most recent 10 out of 59 publications