Induction of Ia antigen in rat epidermal cells and gut epithelium by immunological stimuli.

Abstract

The expression of Ia antigen in rat keratinocytes and gut epithelium was found to be inducible by a variety of immunological stimuli. Graft-vs.-host disease (GvHD) was accompanied by the appearance of Ia antigen in both sites, whereas local immunological stimuli, such as a contact-sensitizing agent applied to the skin and Trichinella spiralis infection of the gut, caused the expression of Ia antigen confined to the sites of contact of these stimuli with the tissues involved. Both T helper and T cytotoxic/suppressor subsets of parental lymphocytes, used to produce GvHD in F1 hybrid recipients, induce Ia expression in the skin and gut of these hosts, but simultaneous removal of both subsets from the donor inocula prevented induction. The Ia antigen expression associated with GvHD was shown to be of host origin but was not acquired from bone marrow-derived cells. Attempts to detect Ia antigen in serum or lymph of rats with GvHD gave negative results, and it was shown that Ia+ cells in the lamina propria of the small intestine did not take up detectable amounts of Ia antigen from the Ia+ intestinal epithelium. It appears that the local recognition of antigen by T lymphocytes can result in the induction of Ia antigen in keratinocytes and in the epithelial cells of the intestine. This antigen is synthesized by the cells in which it is found, and the observation that immunological stimuli are responsible for its appearance suggests that its role is an immunological one. Failure to find evidence that the gut epithelium Ia antigen was transferred to lymph or taken up by other Ia+ cells in the intestinal villi supports the view that this Ia (and, by analogy, that found in keratinocytes) serves a local function, and the possibility that it is involved in antigen presentation to T cells is discussed.

Gut injury in mouse graft-versus-host reaction. Study of its occurrence and mechanisms.

“…This also agrees with the appearance of Ta on various cell types, including gut epithelium, in rats injected with selected subsets of semi-allogeneic T lymphocytes (39). In contrast, IL3 release is consistently higher with L3T4+ than with Lyt 2+ cells, a fact which correlates well with the appearance ofgut MCs in GVHR elicited in nonirradiated mice (since MC precursors are radiosensitive); MCs, which differentiate from precursors present in the gut wall under the effect of IL3 release (7,40) Finally, the arrival of donor T cells in the host mucosa has effects other than the elicitation of epithelial damage.…”

Graft-vs.-host disease elicits expression of class I and class II histocompatibility antigens and the presence of scattered T lymphocytes in rat central nervous system.

“…This level of expression, while well below that seen in the GvHD rats, exceeded that seen in the negative controls that were not reconstituted. In ... cells in gut, skin, and other tissues that do not normally exhibit it (34). GvHD induced in neonatal animals affects the development of normal cerebellar morphology and neuronal maturation (35); however, the mechanism by which this occurs remains unknown.…”

Three-dimensional structure of the rat intestinal wall (Mucosa and submucosa).

“…It is also observed that about 5% of the intestinal absorptive cells penetrate the basal lamina in reverse, protruding their processes into the lamina propria; here a similar association of the absorptive cells with the cells of the immune system takes place. In this context, it is noteworthy that the intraepithelial lymphocytes are mostly T cells in the mouse, rat and human (FERGUSON, 1977;SELBY et al, 1981;LYSCOM and BRUETON, 1982;DILLON and MACDONALD, 1984), and that the absorptive cells of villi possess major histocompatibility complex (MHC) la antigens that are essential for antigen recognition by T cells (SCOTT, 1980;BARCLAY and MASON, 1982;MAYRHOFER et al, 1983 either hydrolytic procedure (DESAKI et al, 1984) or enzymatic digestion (Fig. 16).…”