Lymphocyte Lineages at Mucosal Effector Sites: Rat Salivary Glands

Abstract

Development of T cell lineages and the role of the thymus as a source of immature T cells in parotid (PG) and submandibular salivary glands (SMG) were studied in Fischer 344 rats using the Thy-1/CD45RC/RT6 expression model. In addition, the phenotypes of salivary gland lymphocytes were compared with other conventional and extrathymic populations. PG mononuclear cells consisted of T cells (38%), B cells (29%), and NK cells (4%). SMG had 19% T cells, 7% B cells, 37% NK cells, and an unusual population of CD3−/RT6+ cells. In comparison with lymph node (LN), both PG and SMG were enriched in immature (Thy-1+) and activated (Thy-1−/CD45RC−/RT6−) T cells. Unchanged percentages of Thy-1+ T cells in PG and SMG following short-term adult thymectomy indicated that immature salivary gland T cells had an extrathymic source. In contrast, thymectomy eliminated LN recent thymic emigrants. SMG had T cells with characteristics of extrathymic populations, expressing TCRγδ+ (28%), the CD8αα homodimer (11%), and NKR-P1A (66%). Many SMG T cells expressed integrin αEβ7. PG T cells resembled those isolated from LN in respect to TCR and CD8 isoform usage, but were enriched in αEβ7+ T cells and in NKT cells. Thus, salivary gland mononuclear cells are composed of a variety of subpopulations whose distributions differ between SMG and PG and are distinct from LN. These studies provide a basis for further investigation of regionalization in the mucosal immune network and are relevant to the design of vaccine regimens and intervention during pathological immune processes.

Salivary Gland NK Cells Are Phenotypically and Functionally Unique

“…Depending on the method of preparation, the NK cell population ranged from ∼9%–30% (Figure 1A and data not shown). These numbers are consistent with other reports of mouse and rat NK cells being more prevalent in non-lymphoid tissues, including the naïve SMG as well as during diseases like Sjogren syndrome (SS) [12], [13], [14]. Enzymatic treatment of the SMG is necessary in order to obtain adequate numbers of lymphocytes for analysis.…”

“…NK cells are critical for the early containment of CMV, and a population of NK cells reportedly resides in the SMG of mice and rats [11], [12]. Despite the presence of a significant NK cell population in MCMV resistant C57BL/6 mice (Figure 1A), high viral titers persist in the salivary gland for several weeks post-infection [5], [6].…”

Long-Term Survival of Composite Hemiface/Mandible/Tongue Allografts Correlates With Multilineage Chimerism Development in the Lymphoid and Myeloid Compartments of Recipients

“…These cells are distinct from cells present in peripheral lymphoid organs and are known to be responsible for regulation and mediation of humoral and cellular immune responses in the mucosal immune network (36). Finally, vascularized bone component (mandible) of the hemiface/mandible/tongue allograft represents third important source of donor-origin cells capable of migration, engraftment, and chimerism induction.…”

A CD28 superagonistic antibody elicits 2 functionally distinct waves of T cell activation in rats

“…Apparently, the JJ316-induced T lymphopenia is not a consequence of a redistribution of cells into extralymphoid organs, but instead, T cells rather seem to be selectively retained in the lymph nodes and spleen. In compliance, JJ316 did not induce a memory phenotype in CD4 + T cells based on the classification by O'Sullivan et al (14,15). Flow cytometric analysis, using antibodies against Thy-1, CD45RC, and RT6.1, revealed unaltered frequencies of naive, activated, and memory T cells in the lymph nodes after 10 hours, suggesting that CD28 superagonistic antibodies do not fundamentally impact T cell identity ( Figure 1C).…”