The relationship between the hypothalamic-pituitary adrenal axis and oral-induced immunosuppression

The effects of hypophysectomy on the immune response in mice orally immunized with sheep red blood cells (SRBC) was investigated. Hypophysectomized and sham-operated animals display elevated serum levels of SRBC-specific IgG. In addition, splenic lymphocytes obtained from hypophysectomized mice (i) exhibit an enhanced blastogenic response to SRBC, (ii) present with a lower frequency of T (thy 1.2⁺) cells and produce more total IgG polyclonal antibody in culture in comparison to splenic lymphocytes obtained from non-operated (control) mice. Peyer's patch (PP) and mesenteric lymph node (MLN) lymphocytes from hypophysectomized animals secreted elevated levels of total IgG compared to saline-treated controls. The culture supernates of splenic lymphocytes obtained from hypophysectomized, sham-operated, and control animals contain interleukin-2 suppressive factors as determined using the CTLL-2 cell line. The suppressive effect mediated by the lymphocyte culture supernates is less apparent on interleukin-4-mediated CTLL-2 proliferation. The culture supernates from PP lymphocytes obtained from hypophysectomized mice contain potent interleukin-2 suppressive factors while PP lymphocyte culture supernates from sham-operated and control mice displayed no suppressive activity. Likewise, culture supernates from MLN lymphocytes of hypophysectomized, sham-operated, and control mice possessed no suppressive factors for interleukin-2- or interleukin-4-mediated CTLL-2 proliferation. Taken together, the identification of suppressive factors in the lymphocyte culture supernates along with the enhanced blastogenic response and serum anti-SRBC IgG levels in hypophysectomized mice suggests neuroendocrine pathways regulate oral-induced tolerance.