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Date of Award

12-1983

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

Professor J. Bienenstock

Abstract

The selective localization in mucosal tissues of lymphoblasts derived from the mesenteric lymph node (MLN) compared to those from peripheral lymch nodes (PLN axial, brachial and inguinal) was studied using an adoptive transfer model in syngeneic CBA/J mice. The localization of lymphoblasts which had been labelled in vitro with ³H-thymidine or ¹²⁵I-deoxyuridine was assessed using autoradiography or radiocounting.

I found that the number of MLN lymphoblasts which localized in the small intestine, lung, Peyer's patches, MLN, PLN, spleen, and liver was directly proportional to the number transferred. This relationship was also present in intestinal epithelium and basal and villus lamina propria and in pulmonary parenchyma, BALT and bronchial epithelium. Even at doses of MLN lymphoblasts which approximated four times the daily output of blasts in thoracic duct lymph, I could not saturate the capacity of these tissues to accommodate MLN blasts, nor was their intra-intestinal distribution altered. Because of this dose relationship it is necessary to control the number of blasts transfered when comparing the localization of lymphoblasts from different organ sources using autoradiography. Thus my dose studies show that, contrary to earlier studies which were not controlled in this manner, MLN blasts do not selectively localize compared to PLN blasts in pulmonary parenchyma. In addition the result suggest that any method of increasing the number of lymphoblasts released from MALT (e.g. by mucosal immunization) or increasing the delivery of these cells to a particular organ (by altering the proportion of the carciac output which it receives) will increase the number of immublasts in a tissue.

Although the enumeration of radiolabelled or fluorescent cells in tissue sections has been used extensively in the literature to assess localization, the variation in these results has rarely been stated. I found that this variation can be quite high and is largely due to the probability of detecting a low number of cells in a small volume of tissue.

I found that the sex of the recipiegt had no effect on the number of MLN lymphoblasts which localized in the small intestine 24 h after transfer. In contrast, initial experiments showed that lymphoblasts from male donors localized two to three times more frequently than those from female donors in the small intestines of recipients of either sex. However this phenomenon disappeared between September 1980 and August 1981 and neither its initial existence nor its subsequent lops have been explained. I found that the gonadal hormone environment in which the MLN lymphoblasts developed did not influence their capability to localize in the small intestine 24 h after transfer. However, I do not know whether this observation relates to the phenomenon of greater localization of male lymphoblasts because this phenomenon had likely already disappeared when the experiments involving hormonally altered donors were performed.

Using autoradiography in a series of experiments analyzing the kinetics of lymphoblast localization, I demonstrated that MLN lymphoblasts selectively localize compared to MLN blasts in the small intestine by 0.5 h after transfer. This suggests that one factor in selective localization is the selective entry of MLN blasts from the vasculature, perhaps mediated by specific receptors on blasts and tissue of localization.

The concentration of MLN lymphoblasts was the same in the lamina propria adjacent to the Peyer's patch and distant from the Patch at both 0.5 and 24 h after transfer. This suggests that lymphoblasts extravasate in the lamina propria rather than extravasating in the Peyer's patch and subsequently migrating into the lamina propria. In addition, the distribution of blasts in the basal and villus lamina propria was the same at 0.5 and 24 h after transfer but labelled cells appeared in the intestinal epithelium after 0.5 h.

The evidence presented in this thesis suggests that the selective localization of MLN lymphoblasts is mediated the vascular endothelium in the lamina propria, perhaps by specific receptors.

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