Lymphoid effector cells in intestinal graft-versus-host reaction

Baca-Trespalacios, Maria Eugenia (1987) Lymphoid effector cells in intestinal graft-versus-host reaction. PhD thesis, University of Glasgow.

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Abstract

The aim of this thesis was to examine some of the lymphoid effector cells which are involved in intestinal cell-mediated immune responses as exemplified by the intestinal phase of graft-verus-host reaction (GvHR). The cells which were studied were natural killer (NK) cells and intraepithelial lymphocytes (IEL), both of in which are found increased numbers during a GvHR. A The first experiments examined whether a GvHR in experimental mice could be used to assess the cell-mediated immune effector potentials of different types of donor lymphoid cell. Both parental MLN and spleen cells caused splenomegaly and enhancement of NK activity in unirradiated F, hybrid mice, but. MLN showed a greater ability to induce the systemic changes of GYHR. This was not merely due to a larger proportion of T cells in MLN but was related to the greater ability of. MLN cells to recirculate into host lymphoid tissues. The induction of spienomegaly and NK cell activation in GvHR were shown to require donor cell proliferation, as these alterations were prevented by treating donor cells with mitomycin C. These findings confirmed that the GvHR could be used to assess donor cell effector potential YLY2 and highlighted the importance of donor cell proliferation and recirculation. The role of donor NK cells in the development of systemic and intestinal GvHR wars examined by using NK cell-deficient beige mice as a source of donor cells. Beige spleen cells were unable to induce either acute or proliferative forms of systemic GvHR In unirradieted mice and could not produce a local GvHR as measured by popliteal lymph node hypertrophy. Furthermore, beige spleen cells induced a milder form of intestinal G-HR than that found after injection of normal, congenic 057B/6 (B6) spleen cells. However beige spleen cells were as efficient as B6 cells in inducing a lethal GyHR in irradiated hosts. Although these results suggested an important role for Nil cells in the effector phase of GvHR, subsequent examination showed that beige mice have an additional defect in the generation of cytotoxic T lymphocytes anu LE Yitng and LE YLY9- In contrast, beige mice had normal Di H responses ia vivo and high proliferative responses in vitro. Therefore, the inability of beige spleen cells to mediate is GvHR in may not only reflect their lack of Ni. cell function but may also be due to an associated defect in T cell function. These findings may also indicate that cytotoxic lymphocytes play an important part in the development of GvHR. The role of IEL in the development of intestinal damage was also approached by studying their alloreactivity in vivo. The data presented here confirmed that IEL were capable of inducing a local GvHR as measured by popliteal lymph node hypertrophy or after intraperitoneal injection. Nevertheless, they failed to I. nduce a systemic GvHR after intravenous injection into irradiated recipients. The fact that donor cells require to an host lymphoid tissue in order to mediate alloreactive immune responses led me to compare the migration pathways of intravenously injected IEL with to those of other conventional lymphoid populations. These studies showed that. I: EL failed to an tar lymphoid tissues in vivo, and accumulated predominantly in the liver. This abnormal recirculation was not due to the procedure used to isolate ILL and could not ha explained by poor viability or low proliferative capacity. Furthermore, [EL did not migrate in yLyg like immature lymphocytes or activated peripheral lymph node cells. In contrast to these findings, IEL had a polarised morphology and an excellent locomotor capacity co vi tEP. These characteristics of activated cells led me to examine if TEL could migrate into sites of inflammation in the same way as other activated lymphocytes. These last series of experiments showed that IEL were able to localise in sites of inflamed skin but failed to accumulate in intestine which had been inflamed by a GvHR or a parasite infection. ogether, my results are consistent with the idea that the heterogenous population of 1. EL contains a large proportion of fully differentiated effector cells.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Allan Mowat
Keywords: Medicine, Surgery
Date of Award: 1987
Depositing User: Enlighten Team
Unique ID: glathesis:1987-73409
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 14 Jun 2019 08:56
URI: http://theses.gla.ac.uk/id/eprint/73409

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