Gut Lymphocyte Phenotype Changes After Parenteral Nutrition and Neuropeptide Administration.

ABSTRACT

OBJECTIVE: To define gut-associated lymphoid tissue (GALT) phenotype changes with parenteral nutrition (PN) and PN with bombesin (BBS). BACKGROUND: PN reduces respiratory tract (RT) and GALT Peyer patch and lamina propria lymphocytes, lowers gut and RT immunoglobulin A (IgA) levels, and destroys established RT antiviral and antibacterial immunity. BBS, an enteric nervous system neuropeptide, reverses PN-induced IgA and RT immune defects. METHODS: Experiment 1 Intravenously cannulated ICR mice received chow, PN, or PN + BBS injections for 5 days. LSR-II flow cytometer analyzed Peyer patches and lamina propria isolated lymphocytes for homing phenotypes (L-selectin and LPAM-1) and state of activation (CD25, CD44) in T (CD3)-cell subsets (CD4 and CD8) along with homing phenotype (L-selectin and LPAM-1) in naive B (IgD) and antigen-activated (IgD or IgM) B (CD45R/B220) cells. Experiment 2 Following the initial experiment 1 protocol, lamina propria T regulatory cell phenotype was evaluated by Foxp3 expression. RESULTS: Experiment 1 PN significantly reduced lamina propria (1) CD4CD25 (activated) and (2) CD4CD25LPAM-1 (activated cells homed to the lamina propria) T cells, whereas PN-BBS assimilated chow levels. PN significantly reduced lamina propria (1) IgD (naive), (2) IgDLPAM (antigen-activated homed to the lamina propria) and CD44 memory B cells, whereas PN-BBS assimilated chow levels. Experiment 2 PN significantly reduced lamina propria CD4CD25Foxp3 T regulatory cells compared with chow-fed mice, whereas PN + BBS assimilated chow levels. CONCLUSIONS: PN reduces lamina propria activated and T regulatory cells and also naive and memory B cells. BBS addition to PN maintains these cell phenotypes, demonstrating the intimate involvement of the enteric nervous system in mucosal immunity.