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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29MH051051-05
Application #
2445527
Study Section
Special Emphasis Panel (SRCM (01))
Project Start
1993-07-01
Project End
1999-06-30
Budget Start
1997-07-01
Budget End
1999-06-30
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Pathology
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Shanks, N; Kusnecov, A W (1998) Differential immune reactivity to stress in BALB/cByJ and C57BL/6J mice: in vivo dependence on macrophages. Physiol Behav 65:95-103
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Zhou, D; Shanks, N; Riechman, S E et al. (1996) Interleukin 6 modulates interleukin-1-and stress-induced activation of the hypothalamic-pituitary-adrenal axis in male rats. Neuroendocrinology 63:227-36
Kusnecov, A W; Shurin, M R; Armfield, A et al. (1995) Suppression of lymphocyte mitogenesis in different rat strains exposed to footshock during early diurnal and nocturnal time periods. Psychoneuroendocrinology 20:821-35
Shurin, M R; Kusnecov, A W; Riechman, S E et al. (1995) Effect of a conditioned aversive stimulus on the immune response in three strains of rats. Psychoneuroendocrinology 20:837-49
Kusnecov, A W; Rabin, B S (1994) Stressor-induced alterations of immune function: mechanisms and issues. Int Arch Allergy Immunol 105:107-21