Delphine M. V. Parrott

ANALYSIS OF THE EFFECTOR FUNCTIONS OF DIFFERENT POPULATIONS OF MUCOSAL LYMPHOCYTES

Lymphocytes separated from the epithelial layer of mouse small intestine, IEL, were tested for their NK cytotoxicity against Yac-1 targets. There was little NK activity in a 4 hour assay, but high activity in an 18 hour assay, and the NK activity of IEL did not parallel that in the spleen in any of the mouse strains tested. Furthermore, IEL exerted a suppressor activity on mouse spleen NK activity. Specific T-cell cytotoxicity appeared in IEL in mice immunized with an intraperitoneal injection of P-815 tumor cells. By contrast with IEL, LPL had little NK or NK suppressor activity, but higher levels of specific T-cell cytotoxicity in tumor-immunized mice than intraepithelial lymphocytes. A high proportion of IEL had granules that stained with Giemsa and Astra blue. Furthermore many IEL carried Lyt-2+ phenotype and no other T-cell surface antigen. Intraepithelial lymphocytes appeared, therefore, to have staining and phenotype characteristics of both granular NK cells and suppressor cells. It was clear that the intestinal mucosa contained populations of immune effector cells that were heterogeneous in nature and function.

The Definition of a Germinal Center Area as Distinct from the Thymus-Dependent Area in the Lymphoid Tissue of the Mouse

It has been observed recently that lymphocyte depletion, often cited as a characteristic of neonatally thymectomized animals, was confined to certain specific areas (thymus-dependent areas) in the lymphoid organs of the mouse, namely around the central arteriole within the splenic follicle and the mid and deep cortex of the lymph nodes (Parrott, De Sousa, and East, 1966). By contrast, the rest of the follicle in the spleen and the outer cortical zone of the lymph nodes, where germinal center development normally occurs, remained primarily uninfluenced by the effects of thymectomy.

Ecotaxis of B Cells in the Mouse

Since our early observation that suspensions of in vitro labelled mouse spleen cells have a distribution pattern within the host’s peripheral lymphoid organs which differs from the pattern of distribution of labelled thymus cells (1) other studies of the migratory patterns of lympho-myeloid cells in a number of species (2, 3) have given support to the concept that mature lympho-myeloid cell populations have the capacity to ecotax (4) i.e. to migrate and arrange themselves in clearly defined microenvironments of the peripheral lymphoid organs.

Locomotion of T cells from patients with cutaneous T-cell lymphoma (Sezary syndrome and mycosis fungoides)

Abstract Peripheral blood T cells from eight patients with cutaneous lymphoma (four each with Sezary syndrome or mycosis fungoides) and T cells from skin tumor of one patient each with Sezary syndrome or mycosis fungoides were studied for their locomotor responses to the chemoattractant, casein. Nonmalignant peripheral blood T cells from each patient with mycosis fungoides moved normally. Malignant T cells from skin tumor of patients with mycosis fungoides or Sezary syndrome did not move in the presence of casein. Peripheral blood malignant T cells (Sezary cells) from three of four patients with Sezary syndrome either moved very poorly or did not move at all. The circulating Sezary cells from the fourth patient with Sezary syndrome responded moderately to the chemoattractant, casein. Two of three patients with Sezary syndrome with poor or no locomotor response of T cells underwent therapeutic leukopheresis without any demonstrable effect on their skin infiltration. The patient whose malignant T cells demonstrated moderate locomotor response to casein had a leukemic blast crisis and at that time her skin became free of malignant cells. A repeat study of her circulating T cells at that time demonstrated almost normal locomotor response to casein. These results demonstrate that the locomotor properties of malignant T cells in patients with Sezary syndrome may have prognostic significance.

THE ROLE OF THE THYMUS IN AUTOIMMUNE DISEASE.

During the last three years the thymus has been promoted to a position of singular distinction in the immunological hierarchy. At the same time it has been delegated the role of prime suspect as far as autoimmune disorders are concerned. This suspicion has arisen because of the clinical association between pathological changes in the thymus and diseases with autoimmune symptoms such as myasthenia gravis and systemic lupus erythematosus. These pathological changes present either as a thymic tumour and/or hyperplastic accumulations of lymphocytes or an occasional germinal centre in the thymic medulla. Weight has been added to the suspicion by the fact that mice of a strain known as the New Zealand Black (NZB) develop autoimmune haemolytic anaemia quite spontaneously ( i , 11) and also show germinal centres and lymphocytic proliferations in their thymus (3, 4) . Further, the hybrid progeny of NZB X NZW mice, according to Helyer & Howie (10, 11), develop lupus nephritis and have positive LE tests.

Introduction: Microenvironments in the Lymphoid System

In the lymphoid system one may define a variety of micro-environments within which various processes take place: a) the initial differentiation of stem cells b) traffic of lymphocytes of different origins c) antigen induced interaction between differentiated cells d) antibody production.