Project Details

Description

DESCRIPTION: (provided by applicant) The protective immune response operative in tuberculous infection is not completely defined. Nevertheless, existing evidence suggest that cellular Th1-mediated immunity plays a critical role in host defense against Mtb. The protective role of Thl cell-mediated immune response in TB is perhaps best illustrated by the enhanced susceptibility to Mtb in individuals with human immunodeficiency virus infection, a disease characterized by profound loss of CD4+ T cells, including the Th1subtype. Recently, work in our laboratory has provided in vitro evidence that Th1 cells selectively undergo CD95-mediated apoptosis. Specifically, CD95-mediated apoptosis in response to CD3/TCR (T cell receptor) complex ligation without engagement of co-stimulatory molecules is observed only in Th1 and not Th2 clones. Therefore, in contrast to Th2 lymphocytes, co-stimulation signals are obligatory to resisting CD95-mediated apoptosis during activation of Th1 cells via engagement of CD3/TCR. Thus activation of Th1 cells by CD3 ligation, a scenario akin to antigen challenge in the absence of co-stimulation, results in apoptosis. Based on these results, we propose to test the hypotheses that i) in tuberculous infection, CD95-mediated Th1 depletion occurs, resulting in attenuation of protective immunity against Mtb, thereby enhancing disease susceptibility; ii) downregulation of the expression of the B7 class of co-stimulatory molecules contributes to Th1 apoptosis. Thus the specific aim of the AIDS-FIRCA proposal is to examine if Th1 apoptosis is occurring in vivo at sites of infection, and if there is a correlation with cytokine production and macrophage costimulation. Specifically pleural fluid and lymph nodes obtained from patients with TB pleuritis and TB lymphadenitis will be investigated. This research will be done primarily at the Tuberculosis Research Centre, Chennai, India.
StatusFinished
Effective start/end date8/15/027/31/09

Funding

  • Fogarty International Center: $1,300.00
  • Fogarty International Center: $39,020.00
  • Fogarty International Center: $39,020.00
  • Fogarty International Center: $40,320.00

ASJC

  • Infectious Diseases
  • Pulmonary and Respiratory Medicine

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