STRESSOR-INDUCED MODULATION OF ANTIGEN-SPECIFIC IMMUNITY

Project Details

Description

Aversive stressors alter cellular and humoral immune measures in rats and
mice. Using rats exposed to an acute (one time) footshock stressor, a
cholera toxin (CT) as antigen, preliminary data has led to the conclusion
that (i) antigen-specific in vitro memory spleen cell proliferation and
serum antibody levels are suppressed only when primary immunization
occurs immediately after the stressor (but not > 24 hrs later); (ii)
stressor exposure of antigen-primed rats 7 days after immunization
results in enhanced antigen-specific spleen cell memory proliferation,
but suppressed non-specific mitogen-induced proliferation. In pursuing
the immunological mechanisms of these stressor-induced effects, the focus
of the proposed experiments will be on the study of accessory cell
function and T cell reactivity to antigen immediately following stressor
exposure. Since the immune response to CT is altered only when footshock
is in close proximity to immunization, stress may alter accessory cell
function. Therefore, Specific aim 1 will address the effects of acute
footshock on (i) antigen presentation by antigen-presenting cells (APC),
and (ii) macrophage (Mo) production of IL-1, IL-6, TNF, TGF, and PGE2.
In addition, the in vivo role of Mo in mediating stressor-induced
suppression of lymphocyte function, will be investigated. Specific aim
2 will examine the effect of stress on T lymphocyte reactivity to antigen
immediately after stressor exposure. Thus, unprimed splenic T cells will
be assayed for (i) proliferative activity to antigen-specific and non-
specific signals in vitro, (ii) the ability of Th1 CD4+ T cells to
secrete IL-2 and IFN-gamma, and Th2 CD4+ T cells to elaborate IL-4 and
IL-6, and (iii) CD4+ and CD8+ T cell helper and suppressor regulatory
function, respectively. These measures represent the major interacting
components of T lymphocyte antigen-specific immune responses, that can
also regulate B cell function, which, as stated above, was suppressed by
footshock at the time of immunization. The proliferative, cytokine, and
regulatory measures for T cell reactivity will also form the basis of the
final series of investigators in Specific Aim 3. These experiments will
test whether acute footshock differentially alters the reactivity of
naive and memory T cells to antigen-specific and non-specific signals.
This will be accomplished by dividing splenic T lymphocytes, from
stressed and non-stressed antigen-primed rats, into OX-22- (memory) and
OX-22+ (naive) populations, and assessing the parameters studied in
Specific Aim 2. Collectively, these studies will generate important
avenues for the investigation of basic immune mechanisms altered by acute
stressor exposure, and facilitate understanding of how environmental
factors, such as stress, can influence the immune response to viral
infections, such as HIV.
StatusFinished
Effective start/end date7/1/936/30/99

Funding

  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health

ASJC

  • Cell Biology
  • Immunology

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