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

  • National Institutes of Health: $39,020.00
  • National Institutes of Health: $40,320.00
  • National Institutes of Health: $1,300.00
  • National Institutes of Health: $39,020.00

ASJC

  • Medicine(all)

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