Experimental autoimmune oophoritis. II. Both lymphoid cells and antibodies are successful in adoptive transfer.

Experimental autoimmune oophoritis can be readily induced by passive transfer of peripheral blood lymphocytes, lymph node cells, spleen cells, T- and B-enriched cell suspensions, immune serum and gamma globulins, from ovary antigen immunized rats to naive recipients. Adoptive transfer was markedly enhanced when recipient rats were injected simultaneously with sensitized lymphoid cells and anti-ovary antibodies. Histologically, this passively induced disease was much the same as the actively induced disease. By syngeneic lymph node assay it was shown that regional lymph nodes of neonatally thymectomized rats did not enlarge upon injection of EAOO lymphocytes which otherwise produced a marked effect in lymph nodes of normal recipient rats. Therefore, it appears that enlargement of the draining lymph node was dependent on the participation of host T cells. The possibility that development of EAOO may involve cooperation between antigen-reactive and effector classes of lymphocytes was discussed.     

Cells involved in the immune response: XXII. The demonstration of thymus-specific antigens in the rabbit

Horse anti-rabbit thymus cell serum (HARTS) was obtained by immunizing a horse with rabbit thymocytes intravenously at weekly intervals for 3 weeks. The horse was bled 2 weeks later and the antiserum was analysed for its cytotoxic activity with respect to the lymphocytes of the various lymphoid organs. It was demonstrated that the cytotoxic activity of the antiserum was several orders of magnitude greater for thymus cells than for cells of the other organs tested. Only thymus and lymph node cells were capable of absorbing the thymocytotoxic activity of the antiserum; however, ten to fifteen times as many lymph node cells as thymus cells were required to neutralize the thymocytotoxic activity of the serum. Absorption of the antiserum with the cells of the other lymphoid organs (spleen, bone marrow, appendix, sacculus rotundus, Peyer's patches and circulating leucocytes) resulted in a slight but significant decrease in the thymocytotoxic activity. At no time was the thymocytotoxic activity completely absorbed with cells of these organs. The cytotoxic activity of the antiserum with respect to the cells of the different lymphoid organs other than the thymus could be abolished following absorption of the antiserum with the cells of any of the lymphoid organs. On the basis of our data, it is concluded that (a) the thymocytes possess two groups of antigens—one thymocyte specific and one common to all rabbit lymphocytes and (b) only the lymph nodes of all the lymphoid organs other than the thymus possess significant numbers of thymus-derived or T-cells. However, the proportion of these cells in the lymph node does not exceed 7–10 per cent, a figure much lower than that found in the lymph nodes of the mouse. Less than 1 per cent of the circulating lymphocytes in the rabbit are T-cells.     

Quantitative analysis of tissue distribution of Ly10-like murine alloantigen(s) with antisera and monoclonal antibodies

Tissue distribution of non-Lyt1.1 ("Ly10-like") antigen or antigens encoded by short chromosomal segment differentiating B6-Ly-1a congenic strain from B6 strain of mice was studied by quantitative absorption of (BALB/c X B6)F1 anti B6-Ly-1a antiserum and by direct cytotoxicity of Ly-10-132-12-26 monoclonal antibody on lymphoid cell populations. Identical strain but not tissue distribution pattern does not allow to conclude whether antiserum and monoclonal antibody detect the same or closely linked antigens. Absorption experiments revealed the highest antigen content in the brain tissue, lower in testis and kidney, still lower in lymphoid organs and the lowest in liver and lung. Among lymphoid cells, bone marrow cells had highest absorbing capacity, followed by thymus, spleen and lymph nodes. Monoclonal antibody lysed almost 100% of thymocytes, 30% bone marrow cells and 10-20% of spleen and lymph node cells (both T-cell and B-cell enriched populations contained the same proportion of positive cells). Cortisone resistant thymocytes showed the same sensitivity as cortical thymocytes to Ly-10-132-12-26 antibody which is distinguishable characteristics of medullary thymocytes from peripheral T cells. Mitogen activated lymphocytes exhibited significantly higher expression of Ly10-like antigen than resting peripheral lymphocytes.     

Age-decrease of cells sensitive to an autoantibody-specific for thymocytes and thymus-dependent lymphocytes in NZB mice

NZB mice naturally produce an autoantibody which in the presence of complement is specifically cytotoxic for thymocytes and thymus-dependent lymphocytes (T-cells) in the peripheral lymphoid tissues (lymph nodes and spleen) and the circulation of mice. Using a direct cytotoxicity test with a NZB mouse serum pool which contained the high titred autoantibody, a progressive decrease was observed with age in the proportion of the autoantibody-sensitive cells in mesenteric lymph node, spleen, and blood of NZB mice in comparison with mice of other strains (C57BL/6J and NZW). The numerical decrease in the population of autoantibody-sensitive cells was evident at younger age and greater degree in the peripheral blood than in the lymph node and spleen. The age-decrease in the number of autoantibody-sensitive cells in lymph node and spleen contrasted with the numerical increase in nucleated cells in these organs. The age-decrease in the proportion and number of the autoantibody-sensitive cells in the blood exceeded the decrease in the blood lymphocyte count. This finding indicated that T-cells in the blood are selectively depleted with the ageing of NZB mice. A similar observation was made on the blood lymphocytes of (NZB × NZW)F₁ hybrid mice. The depletion of T-cells in the blood in association with the production of natural thymocytotoxic autoantibody is termed autoimmune thymus-dependent lymphocytopenia.     

Local immunity in lung-associated lymph nodes in a murine model of pulmonary histoplasmosis.

Local immunity against acute pulmonary histoplasmosis was studied in the lung-associated lymph nodes of normal nonimmune mice infected intratracheally with live Histoplasma capsulatum yeasts. The phenotypes and distribution of cells in lung-associated lymph nodes and spleens were determined by flow cytometry. In addition, the immune responsiveness of these cells was evaluated by in vitro blastogenesis. Anti-H. capsulatum antibodies in serum and H. capsulatum antigen in tissue were measured by immunoassays. Cellular immune responses were greater in the lymph nodes than in the spleens. In lymph nodes 7 days after infection, a marked increase in the number of B lymphocytes caused the percentage to rise to 43%, compared with 26% in controls, and it remained elevated throughout the course of infection. A CD3+ cell that did not express CD4 or CD8 increased in number until it constituted 21% of lymph node cells, compared with 5% in controls, by day 14. The numbers of CD4+ and CD8+ T lymphocytes were modestly increased from days 7 to 35, but their percentages dropped because of the greater numbers of B lymphocytes and CD3+4-8- cells. Macrophages consistently constituted 2 to 3% of lymph node cells during the study. In spleens 7 days after infection, the percentage of macrophages in infected mice rose to 21%, compared with 9% in controls, but the total spleen cell number did not increase until day 14, when all cell subsets were nearly double in number. The in vitro blastogenic response of lymph node cells to H. capsulatum peaked at day 7, but spleen cell response was minimal during the course of infection. Histoplasma-specific serum immunoglobulin G antibodies reached peak levels by day 21 and remained high to the end of the study. In contrast, levels of antigen-specific immunoglobulin M antibodies were very low. These data suggest that antigen-specific immune responses occur in lung-associated lymph nodes and that this draining lymph node response may be an important component in host defense against Histoplasma lung infection.     

The cells involved in cell-mediated and transplantation immunity in the normal outbred rabbit. X. The organ sources of the stimulator and responder cells in the mixed leukocyte culture reaction.

This investigation is concerned with the elucidation of the organ distribution of stimulator and responder cells in the one-way MLR (mixed leukocyte reaction). The organs investigated were the thymus, bone marrow, spleen, lymph nodes, appendix, sacculus rotundus, Peyer's patches and the circulation. Mitomycin-C treated bone marrow cells and WBC were used as stimulator cells to investigate, in a systematic fashion, the blastogenic responses of the responder cells of the allogeneic lymphoid organs. Responses occurred optimally on day 5 of culture and were dependent upon responder cell concentration. Peyer's patches and mesenteric lymph node cells responded to a greater extent than the cell of any of the other lymphoid organs. Rabbit WBC responded consistently in the one-way MLR, in contrast to the findings of other investigators. Cells of the thymus and bone marrow cultured individually or in combination did not respond. The cells of the different lymphoid organs were investigated as to their stimulator cell activity. Responder WBC or spleen cells were cultured with the mitomycin-C treated stimulator cells. On a per cell basis, the cells of the Peyer's patches, spleen and mesenteric lymph nodes were the most potent stimulator cells. There was no correlation between stimulating capacity and the percentage of stimulator cells bearing surface immunoglobulins. Thus, the stimulating capacity of these cells in the one-way MLR is not a reflection of, or dependent upon, surface immunoglobulins. A consistent finding was an MLR-like response of spleen cells and WBC cultured with autologous mitomycin-C treated Peyer's patches, sacculus rotundus or appendix cells.     

Response of rat blood, spleen, and lymph node leucocytes to soluble and insoluble antigen

Solubilized sheep erythrocyte stroma was found to be antigenic in rats. Spleen and lymph nodes of rats injected with this antigen contained more 7S than 19S plaque-forming cells throughout the primary and secondary responses. When compared to the primary response, secondary immunization with this antigen elicited increased numbers of both 19S and 7S plaque-forming cells. Antibody synthesizing leucocytes in the blood during the primary and secondary responses were predominantly 7S producers during the first few days. Later 19S producers predominated.

Intact sheep erythrocytes elicited the same pattern of 19S and 7S antibody-forming cell development in the lymph nodes and blood of intravenously injected rats, but during the early primary response in the spleen there was a predominance of 19S over 7S plaque-forming cells. The 7S cells were in a majority during the entire secondary response of the spleen to intact erythrocytes. The secondary response of spleen and lymph node to intact erythrocytes showed an elevated 7S plaque forming cell response but the number of 19S cells was similar to that detecred after primary immunization.

The appearance of haemolytic and haemagglutinating 19S and 7S antibody to sheep erythrocytes or solubilized stroma generally reflected the cellular picture of the spleen. By using an anti-7S globulin it was found that 19S and 7S antibody appeared simultaneously in the serum.

After immunization of rats with intact erythrocytes or solubilized stroma the number of lymphoid cells that took up tritiated thymidine was about one hundred-fold greater than the number of antibody-forming cells as determined by localized haemolysis in gel. The number of lymphoid cells positive in an immunocyto-adherence assay was more closely related to the number of cells taking up tritiated thymidine.

The passive transfer of spleen cells from rats immunized to sheep erythrocytes showed the number of circulating antibody-forming cells in the normal and irradiated recipients to be related to the concentration of antibody-forming cells localizing in the recipient spleen. The number of antibody-forming cells in the peripheral blood was greater in splenectomized recipients. Irradiation had no effect on the number of antibody-forming leucocytes in the circulation of the splenectomized recipients.

     

The circulatory behaviour of normal and enzyme altered thymocytes in rats

The circulation of rat thymocytes and factors which may control their pathway were studied. Evidence was obtained that intravenously infused thymocytes migrate from blood to spleen and lymph nodes in a manner similar to lymphocytes, though in lesser amounts. Thymocytes, incubated with neuraminidase prior to intravenous infusion, exhibit markedly altered cell migration. Enzyme-treated thymocytes concentrate in the liver with little accumulation in the spleen. Subsequently, however, small numbers of cells migrate to lymph nodes. Trypsin treatment does not alter the migratory pathway of thymocytes. The results suggest that thymocytes migrate from blood to peripheral lymphoid tissue and that sugar constituents may determine the circulatory pathway.     

Production of Lymphocytes and Plasma Cells in the Rat following Immunization with Human Serum Albumin

The lymphoid tissue response to immunization with human serum albumin has been studied in rats. No change was found in the total circulating blood lymphocytes or the hourly output of lymphocytes from thoracic duct fistulae in the immunized rats compared to the controls. The number of cells in the thoracic duct lymph synthesizing DNA was the same in the two groups of rats. The specific activities of the spleen DNAP and RNAP and the lymph node RNAP were significantly higher in the immunized rats.

A considerable proliferation of the plasma cells occurred in the nodes and spleen of the immunized rats. Evidence is presented to show that the mature plasma cell is an end cell and that there is a high rate of turnover of these cells in the nodes. The analysis of the DNAP and RNAP specific activity results is discussed in relation to the inert and active DNA mass in the tissue. Observations have been made on the effects of giving Freund's adjuvant alone to rats, in particular the cystic changes that occurred in the caecal nodes.

     

T and B Cells in Various Lymphoid Tissues in Mice: Membrane Immunofluorescence with Purified Lymphoid Cells

The proportion of T and B cells in several lymphoid tissues of the mouse was determined by membrane immunofluorescence. Lymphoid cell preparations were purified by glass-wool column and Hypoque-Ficoll sedimentation to eliminate the large majority of non-lymphoid cells which might introduce counting errors on fluorescence microscopy. FITC-labelled horse anti-mouse-globulin did not stain thymocytes (T cells) whereas it did stain a proportion of the lymphocytes of other lymphoid tissues (B cells): peripheral blood, 11%; bone marrow, lymph node, 23%; spleen, 24%. These results correlated well with the proportion of cells stained by anti-B cell sera obtained by the complete absorption of anti-lymphocyte serum (ALS) with thymocytes.     

Antigenic correlations between brain and thymus. I. Common antigenic structures in rat and mouse brain tissue and thymocytes

Rabbit anti-mouse brain serum (AMBS) and anti-rat brain serum (ARBS) were found to exhibit cytotoxic activity against homologous thymocytes. AMBS also proved to be cytotoxic for rat thymocytes and ARBS for mice thymocytes. Although rat lymph node and spleen cells were nearly uneffected by ARBS, AMBS exhibited some cytotoxicity against the lymph node and spleen cells of mice. The percentage of mouse lymph node and spleen cells lysed by AMBS resembled that caused by Θ-isoantiserum, Nevertheless, unlike Θ-isoantisera, the AMBS was also cytotoxic for AKR thymocytes. Absorption analyses showed that the cytotoxic activity on mouse thymocytes could be absorbed out of the ARBS by both rat and mouse thymocytes and brain residues, However, the latter failed to remove cytotoxic effects on rat thymocytes. Conversely, rat thymocytes and brain homogenate did not influence the cytotoxic effects of AMBS on mouse thymocytes, but eliminated its cytotoxic effects on rat thymocytes. After previous in vitro treatment with anti-CBA mouse brain serum or ARBS, CBA brain residue proved no longer capable of absorbing any Θ-C3H isoantibodies. This indicates that the antibrain antibodies had blocked the Θ-determinants.     

Immunodepression in trypanosome-infected mice. VI. Comparison of immune responses of different lymphoid organs

Mitogen stimulation of cells from various lymphoid organs of C3H/He mice chronically infected with an isolate of Trypanosoma congolense was studied at different time intervals after infection, using concanavalin A (Con A) and lipopolysaccharide (LPS). At the same time, changes in the percentages of T, B and null lymphocytes in these organs were determined by immunofluorescence staining. The responses of T and B lymphocytes in the spleen were totally depressed, and the cellular composition was drastically altered by day 14 after infection. Unlike the spleen, the lymph nodes showed minor changes in their T and B lymphocyte responses and cell composition during the course of the infection, except the B cell response and composition which were altered late in the infection. The thymus and bone marrow did not show any appreciable changes in their mitogen responses and cell composition throughout the infection. The peripheral blood lymphocytes showed reduced B cell responses. Spleen cells from chronically infected mice suppressed lymphocyte stimulation induced in normal spleen and lymph node cell populations by Con A, LPS and allogeneic stimulator cells. Lymph node cells from the same group of mice did not exhibit any such suppressor activity. In the experimental system used here, the spleen is the primary site of immune depression, and other lymphoid organs such as the lymph nodes and thymus are very little affected.     

Duration dependent effect of chronic stress on primary and secondary lymphoid organs and their reversibility in rats

The present study was undertaken to investigate whether or not chronic stress effect and its reversibility on lymphoid organs is duration dependent. Male rats were exposed to restraint (1?h) followed by a gap of 4?h to forced swimming exercise (15?min) daily for 2, 4 and 8 weeks. After each exposure period, rats were allowed to recover for 6 weeks. Stress exposure resulted in duration dependent decreases in weight of thymus and axillary lymph nodes, lymphocyte counts of spleen, thymus and axillary lymph nodes and number of islets of white pulp of spleen and increases in apoptotic index of splenocytes, thymocytes and lymphocytes of axillary lymph nodes. All the parameters of lymphoid organs studied showed significant alterations in 2 weeks of stress exposure indicated their sensitivity to stress effects in short term exposure and thymus was the most sensitive organ among all. The alterations in all the parameters of spleen and majority of parameters of thymus and axillary lymph nodes returned to control level in recovery group rats of 2 and 4 weeks exposure but not in that of 8 weeks exposure. The present study for the first time reveal that severity of stress effects on lymphoid organs increases with increasing duration of exposure and shorter the exposure period faster the recovery. In addition, an in vitro study showed that corticosterone caused apoptosis of thymocytes, splenocytes and lymphocytes of axillary lymph nodes in dose dependent manner. Thus corticosterone induced death of cells of lymphoid organs under stress is the major cause of involution of lymphoid organs.     

The Effects of Metallic Tin on Background Plaque-Forming Cells, Immunoglobulins and the Immune Response

Inoculation of metallic tin powder into Lewis rats resulted in marked enlargement of the draining lymph nodes. Plasma cells were the major contributors to the increase in cell mass. Certain immunologic aspects of this plasma cell lymphadenopathy were investigated. Immunoglobulin isotypes were distinguished and quantitated by fluorescence immunocytochemistry and rocket electrophoresis of lymph node extracts. Background plaque-forming cells directed against sheep red blood cells were increased. Specific activity was highest 4 days after inoculation of tin. Lymph nodes and spleen continued to increase in cell number so that total background activity attained a maximum at 14 days after inoculation of tin. Tin was a good adjuvant for plaque-forming cells in lymph nodes and for serum agglutinins (primary and secondary responses) when the rats were immunized with sheep red blood cells, even when the antigen was injected at a remote site. The plasma cell response to tin may be due to local polyclonal activation.     

Diabetogenic T cells are primed both in pancreatic and gut-associated lymph nodes in NOD mice

Activation of an islet-specific immune response is an early yet essential step in autoimmune diabetes. The immune cells and antigen(s) involved in this early step and its anatomical site remain incompletely understood. To directly evaluate the site where islet-specific and diabetogenic lymphocytes are activated, we isolated lymphocytes from spleen and from pancreas-draining, gut-associated and subcutaneous lymph nodes of diabetic NOD mice and of young NOD mice, and transferred these into NOD scid/scid recipients devoid of endogenous islet-specific immune responses themselves. Although spleen lymphocytes from diabetic NOD mice induced diabetes more rapidly than lymphocytes from any other lymphoid tissue, spleen lymphocytes from young NOD donors were not superior to other lymphocytes from the same donors. At a donor-age of 6 weeks, the most-diabetogenic lymphocytes were found in pancreas-draining lymph node whereas gut-associated lymph nodes and the spleen were sources of intermediate diabetogenic activity. Lymphocytes from peripheral lymph nodes were only weakly diabetogenic at this age, and also remained the least efficient later. Surprisingly, lymphocytes isolated even from 3-week-old NOD mice had diabetogenic potential. However, such cells were almost exclusively found in gut-associated lymph nodes. This suggests that initial priming of diabetogenic cells takes place in the gut whereas pancreas-draining lymph nodes may serve as the site of amplification of the autoimmune response.     

Th17 cells induce ectopic lymphoid follicles in central nervous system tissue inflammation

Ectopic lymphoid follicles are hallmarks of chronic autoimmune inflammatory diseases such as multiple sclerosis (MS), rheumatoid arthritis, Sj?gren's syndrome, and myasthenia gravis. However, the effector cells and mechanisms that induce their development are unknown. Here we showed that in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, Th17 cells specifically induced ectopic lymphoid follicles in the central nervous system (CNS). Development of ectopic lymphoid follicles was partly dependent on the cytokine interleukin 17 (IL-17) and on the cell surface molecule Podoplanin (Pdp), which was expressed on Th17 cells, but not on other effector T cell subsets. Pdp was also crucial for the development of secondary lymphoid structures: Pdp-deficient mice lacked peripheral lymph nodes and had a defect in forming normal lymphoid follicles and germinal centers in spleen and lymph node remnants. Thus, Th17 cells are uniquely endowed to induce tissue inflammation, characterized by ectopic lymphoid follicles within the target organ.     

Dipeptidyl peptidase IV (DP IV) activity in serum and on lymphocytes of MRL/Mp-lpr/lpr mice correlates with disease onset.

DP IV (CD26), a serine protease expressed on activated T cells, participates in immune responses in vivo as well as in vitro. We measured cell surface and serum DP IV in mice of the autoimmune MRL/Mp-lpr/lpr (MRL/l) strain, which is characterized by massive T cell proliferation and production of anti-nuclear autoantibodies. The mass of inguinal lymph nodes correlated with serum DP IV activity. Furthermore, serum DP IV activity increased markedly in parallel with the acceleration of lymph node swelling and anti-nDNA antibody production. Serum DP IV activity in 16-week-old MRL/l mice reached levels up to three higher than those in age-matched MRL/Mp- +/+ mice or BALB/c mice. Immunohistochemical staining and flow cytometric analysis identified DV IV on surfaces of lymphocytes from the enlarged lymph nodes of MRL/l mice. Subcutaneous injection of the mechanism-based inhibitor, Pro-boroPro, reduced protease activity in serum and cell suspensions prepared from spleen and lymph nodes, confirming the identity of the enzyme as DP IV. These results indicate that the massively accumulating lymphocytes of MRL/l mice have a property characteristic of activated T cells, although they express little surface CD4 or CD8 and do not produce IL-2. DP IV may participate in the role these cells play in the pathogenesis of MRL/l autoimmune disease.     

Lymphoproliferative responses and protection in conventional piglets inoculated orally with virulent or attenuated porcine epidemic diarrhoea virus

Lymphocyte proliferative responses were evaluated in mucosal (mesenteric lymph nodes) and systemic (spleen and blood) lymphoid tissues of conventional piglets inoculated with the virulent or attenuated isolates of porcine epidemic diarrhoea virus (PEDV) strain CV-777 and challenged 21 days later with the virulent isolate of the same virus. A lymphoproliferative assay was developed in which mononuclear cells isolated from lymphoid tissues at different postinoculation and postchallenge days underwent a secondary in vitro stimulation with semipurified antigen obtained from PEDV-infected cell cultures. Vigorous lymphocyte proliferative responses were detected in the pigs inoculated with the virulent PEDV at postinoculation days 4-21, especially in the mesenteric lymph nodes and the blood; however, in the spleen this response was lower and less regular. The pigs inoculated with the attenuated virus showed a less intense response, the higher lymphocyte proliferation also corresponded to the mononuclear cells from mesenteric lymph nodes. Lymphocyte proliferation responses showed high correlations with protection against homologous challenge with virulent PEDV, and this correlation was higher in the gut associated lymphoid tissues (mesenteric lymph nodes). The cell proliferation response detected in blood mirrored that detected in the mesenteric lymph nodes, and showed also good correlation with protection. The results confirm that T-cell-helper function, assessed by lymphocyte proliferation responses, contributes to establishing a protective immune response against PEDV infections.     

Electrophoresis of Lymphoid Cells

The electrophoretic mobility of small lymphoid cells in the thymus, lymph nodes, and spleen was measured. The distribution patterns were organ specific. The majority of the thymic cells were slow with a small 'tail' of faster cells. Both lymph node and spleen cells showed a fast and a slow cell population with a difference in mean electrophoretic mobility of about 40%. The percentage of cells to the fast and slow groups was similar to the percentage of T- and B-cells in these organs It is therefore suggested that T-and B-cells may be characterized by their different electrophoretic mobilities and also that there may be a change in the net surface charge during maturation from thymocyte to T-lymphocyte.     

Organ distribution of natural cytotoxicity in the rat.

The natural (spontaneous) cytotoxicity (NC) of cell populations from different lymphoid organs of the rat were examined using a human myeloid cell line (K562) and a rat fibrosarcoma cell line (Mc40) as target cells. Rat blood and spleen lymphoid cell populations gave high cytotoxicity against K562, while lymph node cells and bone-marrow cells gave low levels of cytotoxicity and thymus cells virtually no activity. Addition of thymus or lymph node cells to spleen effector cells did not suppress the high cytotoxicity of spleen cells. A similar organ distribution of reactivity was observed against Mc40 cells, but the levels of cytotoxicity were much lower than for K562. A strain difference was monitored in the levels of natural cytotoxicity and cell populations from inbred Wistar rats consistently gave higher activity on a cell-to-cell basis than the corresponding population from PVG/c rats. Natural cytotoxicity was not removed when spleen cell populations were depleted of cells adhering to nylon-fibre columns or plastic surfaces, or depleted of cells ingesting carbonyl iron. In agreement with other studies using human and animal lymphoid cells, the natural killer cell in this system was found to be non-adherent and non-phagocytic and its distribution did not correspond to the established organ distribution of T or B lymphocytes.