Margaret J. Dallman

Functions of rat T-lymphocyte subsets isolated by means of monoclonal antibodies.

The morphological homogeneity of lymphocytes contrasts strongly with their functiona! heterogeneity, and there can be few mammalian cells whose unremarkable appearance more completely conceals such a wide diversity of activities. The major partition of these cells into the B and T cell sets was originally made on an anatomical basis (Mitchell & Miller 1968), but it was the demonstration that lymphocytes with different functions expressed different serologically defined cell membrane molecules (Raff 1971, Cantor & Boyse 1975) that made possible detailed studies of functional specialisation amongst lymphocytes. This serological approach to the problem of identifying lymphocyte subpopulations has been made much more powerful by the development of monoclonal antibodies and these reagents have become the primary tools of those studying lymphocyte heterogeneity. In this article a number of monoclonal antibodies are described that were derived by cell fusion between the NSI mouse myeloma (Kohler & Milstein 1976) and splenocytes from mice immunised with rat lymphocyte membrane antigens. These antibodies have allowed the defmition of three non-overlapping subsets of rat T lymphocytes and it has been shown that this phenotypic heterogeneity corresponds to a functional one. By using these antibodies to stain cryostat sections of rat thymus and by evaluating the functional activities of thymocytes some indication of possible maturation pathways within the thymus have been obtained. This review contains hitherto unpublished work together with that which has already appeared in published articles.

Cytokines as mediators of organ graft rejection and tolerance

The analysis of cytokines following organ transplantation continues to flourish as a major area of investigation for transplant biologists. Over the past year many papers have reported the use of both molecular and antibody-based tools to dissect the expression of cytokines during graft rejection in both experimental and clinical transplantation. Further, how the expression of cytokines is altered during the induction of tolerance has been investigated by several groups.

Cytokines and peripheral tolerance to alloantigen

The induction of peripheral tolerance to alloantigen is accompanied in many cases by a decrease in the production of cytokines such as IL-2 and IFN gamma, yet a sustained production of cytokines such as IL-10 and IL-4. Whether or not this altered pattern of cytokine production in tolerant animals is causally related to the induction and/or maintenance of the tolerant state has yet to be fully determined, although experiments blocking selectively the action of IL-2 with CD25 antibodies suggest that manipulation of cytokine production may at least be a route to tolerance. Alternative methods for directly influencing the cytokine balance are sought and recent experiments on the CD28/CTLA-4-B7 interaction suggest a possible approach.

Vascular anastomotic techniques for experimental intestinal transplantation

A comparison of two techniques for the vascualr anastomosis of intestinal transplants in the rat suggests that the use of an aortic segment with the graft leads to reduced operative time and improved technical success.