Noradrenergic sympathetic innervation of the spleen: I. Nerve fibers associate with lymphocytes and macrophages in specific compartments of the splenic white pulp

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Abstract
Sympathetic noradrenergic nerve fibers, stained with antiserum for tyrosine hydroxylase (TH), richly innervate the splenic white pulp. These fibers distribute with the vascular and trabecular systems, and associate mainly with the central artery and its branches, the periarteriolar lymphatic sheath (PALS), the marginal sinus, and the parafollicular zone, with occasional delicate fibers also present in the follicles. Simultaneous staining of TH-positive nerve fibers and markers for specific lymphoid cells has shown several regions of contact between nerves and lymphocytes or macrophages. The TH-positive nerve fibers in the plexuses around the central arterial system and in the PALS are present among T lymphocytes (OX-19-positive cells) including both T helper and T suppressor cells, and interdigitating cells. At the marginal sinus, TH-positive fibers run adjacent to macrophages (ED3-positive cells), B lymphocytes (IgM-positive), and intensely fluorescent IgM-positive cells. Along the parafollicular zone, TH-positive nerve fibers run adjacent to T lymphocytes, peripheral follicular B lymphocytes, and intensely fluorescent IgM-positive cells. Within some follicles, delicate fibers end adjacent to both T and B lymphocytes. These relationships suggest a direct interaction between norepinephrine release from the TH-positive nerve terminals and the lymphocytes and macrophages closely associated with them, and focuses attention on the potential neural modulation of related functions such as T and B lymphocyte entry into the spleen and antigen capture (marginal zone), antigen presentation and T cell activation (PALS), B cell activation (parafollicular zone and marginal zone), and lymphocyte egress (outer marginal zone).