Humoral Immune Response in Mice Over-expressing or Deficient in Growth Hormone

Abstract

Effects of growth hormone (GH) levels on the humoral immune response were investigated in metallothionein I (MT)-bovine (b) GH-transgenic (tg) and GH-deficient Ames dwarf (Prop1 dt–/–) mice. Four-month-old mice were given primary and secondary injections of either normal saline or tetanus toxoid (TT) to induce specific antibody (Ab) production. MT-bGH-tg mice with high peripheral levels of bGH produced less TT-specific Ab than normal nontransgenic (Ntg) littermates, df, or nondwarf (Ndf) control mice. Titers reached maximum levels at 3–4 weeks postprimary immunization (PPI) and declined gradually through 24 weeks PPI in all groups of mice. Peripheral CD4+ and CD8+ T cell populations were significantly lower in tg than in Ntg, df, or Ndf mice. No significant differences were found in B cell numbers between tg, Ntg, or df mice. T helper 2 (Th2) cell populations were significantly greater in df mice compared to Ntg control mice. No significant differences were found in CD4+:CD8+ T cell ratios, interleukin (IL)-4 concentrations or interferon (IFN)-γ levels between tg, Ntg, df, and Ndf mice. No patterns of significant sexual dimorphism were found for any of the immune parameters studied. Elevated levels of corticosterone were investigated as a possible immunosuppressant mechanism responsible for low Ab responses in the tg mice. Ab production was not enhanced by decreasing corticosterone in tg mice. Thus, high endogenous GH levels inhibit specific Ab production and peripheral T cell populations but not peripheral B cell numbers, Th2 cell populations, or IL-4 or IFN-gamma production. Elevated corticosterone levels do not appear to be responsible for suppressed humoral immune responses. Low levels of endogenous GH do not inhibit specific Ab production but may contribute to increased peripheral Th2 cell numbers.

GH and ageing: Pitfalls and new insights

“…This likely represents a shift in the distribution of food-derived energy toward other energetically costly processes and in particular, thermogenesis [94]. However, these animals exhibit normal antibody production in response to a strong challenge [95] and exhibit a delay in immunosenesence [21, 88]. …”

Energy restriction restores the impaired immune response in overweight (cafeteria) rats

“…The supernatant was discarded and cells were resuspended in 500 L of PBS. Cells stained with monoclonal antibodies were analyzed by flow cytometry with a FACScan Cell Sorter (Becton Dickinson, Mountain View, CA) as previously described [11,29]. For each experiment 5,000 cells with the forward and 90°light scattering characteristics of mononuclear cells were analyzed.…”

“…NK cells were isolated from peripheral blood as previously published [29]. NK cells (Effector cells; E) at a concentration of 5 ϫ 10 6 cells/mL were mixed with target cells (K562) with concentration of 1 ϫ 10 5 cells/mL at the final E:T ratio of 25:1.…”

“…Cells were analyzed with the flow cytometer immediately after the incubation with DNA staining solution, using the blue-green excitation light (488 nm) with a FACScan Cell Sorter and LYSIS-II software (Becton Dickinson, USA). The percentage of killed target cells or specific cytotoxicity (%) was determined by subtracting the dead cells in incubated target cells alone from the percentage of killed target cells in the test samples [29,30].…”

Voluntary wheel-running exercise enhances antigen-specific antibody-producing splenic B cell response and prolongs IgG half-life in the blood

“…This contradiction may be explained by the exercise period (10 months) resulting in aging of B-lymphocytes contributing to the age-related decline in the immune response (Souvannavong et al 1998). A previous study showed that TTspecific antibody titers increased without B cell (CD19 + ) density changes in the peripheral blood (Hall et al 2002). However, increased TT-specific antibody-producing cells (Fig.…”