The CD56 adhesion molecule is the major determinant for detecting non‐major histocompatibility complex‐restricted cytotoxic mononuclear cells from the intestinal lamina propria

Abstract

In this study, specific antibodies against natural killer (NK) cell surface markers identify these cells to be commonly present in normal intestinal mucosa of inflammatory bowel disease (IBD) and carcinoma patients. Cells expressing the CD56 adhesion molecule were found to be far more abundant than CD16+ cells. Functional studies revealed that cells mediating non-major histocompatibility complex-restricted cytotoxicity (NK activity) in the lamina propria express the CD56 surface antigen, whereas only a minority of this activity resides in the population with CD16 expression. This is in contrast with peripheral blood NK cells, which were found to be almost exclusively both CD16+ and CD56+. Moreover, in the lamina propria of the intestine we found CD3+ T lymphocytes not to be involved in spontaneous cell-mediated killing of tumor cells. Considerably higher numbers of cells with the CD16 or CD56 surface markers were found to be present in normal mucosa of IBD patients compared with normal mucosa of carcinoma patients, which was also reflected in higher levels of cytotoxicity detected in lamina propria mononuclear cell preparations from normal IBD mucosa. Because of the disease-related localization of the mucosa studied from both patient groups, i.e. ileum vs. colon, the observed differences may be related to tissue characteristics. Within the IBD group, relatively high levels of cytotoxicity were found in cell preparations from normal mucosa of Crohn's disease patients compared with ulcerative colitis patients, which might support the current concept that Crohn's disease affects the whole of the gastrointestinal tract.

CD56 Marks an Effector T Cell Subset in the Human Intestine

“…2C). Although granular phenotype may suggest cytolytic potential, significant CD56 ϩ T cell cytotoxicity was not detected in our experiments (data not shown) or other studies (37,41).…”

“…ϩ or CD56 Ϫ effector T cells) (41). Although depletion experiments suggested a similar effector function for the CD161 ϩ T cell subset, we did not detect consistent effector function for this subset in our coculture experimental setting (data not shown).…”

“…CD56 ϩ T cells effectively induced responder T cell proliferation and IFN-␥ production (Fig. 7) while not decreasing responder cell survival (data not shown) (37,41). Interestingly, responder T cell activation was not driven by enhanced proinflammatory cytokine production by CD56 ϩ T cells (Fig.…”

“…Preferential IFN-␥ and TNF expression profiles, but marginal expression of regulatory cytokines such as IL-13, IL-4, IL-5, and IL-10 ( Fig. 3) (36), or significant CTL activity (41), specifically support a proinflammatory effector function, and clearly distinguish CD56 ϩ T cells from the NKT subset (33). Notably, we directly demonstrate an enhanced effector potential for CD56 ϩ T cells by using a unique in vitro culture system that permits analysis of effector-responder interactions.…”

Lamina Propria Mononuclear Cells Express and Respond to Interleukin-2 Differently in Crohn's Disease and Ulcerative Colitis.

“…In this study CD-derived LPMCcontained more CD56+ lymphocytes, especially CD3+, CD56+lymphocytes, and UC-derived LPMChad fewer CD3+, CD56+and CD3~, CD56+lymphocytes compared with control cells, when freshly isolated LPMCwere analyzed in the flow cytometry. Van Tol et al also demonstrated that non-MHC restricted cytotoxicity mediated by CD56+ lymphocytes was increased in CD LPMCcompared with UC LPMC (19). Taken together, the numerical alteration in LAKprecursors among mRNAwas enhanced in freshly isolated LPMCfrom the inflamed mucosa with CDthan in control LPMCbut there was no significant difference in IL-2 mRNA levels between the cells from the diseased mucosa with UCand control cells.…”