Circulating T and B lymphocytes of the mouse. I. Migratory properties

Studies on the identity of thoracic duct lymphocytes (TDL⁴) from normal and T cell-depleted mice indicated that as many circulating B lymphocytes were produced by healthy T cell-depleted mice as normal mice. Proportions of T and B cells from the thoracic duct of CBA mice changed markedly during the first 4 days of drainage from 82% T cells and 16% B cells at 12 hr to approximately equal proportions of both classes after 3 days. In absolute terms, T cells were mobilized rapidly by thoracic duct drainage and B cells very slowly. Histologically, this was reflected in a rapid depletion of the T cell-dependent areas of the lymphoid organs. The B cell-dependent areas, in contrast, became depleted of lymphocytes only after drainage for a week or more.The homing properties of circulating lymphocytes were investigated using TDL from normal and T cell-depleted mice as relatively pure sources of T and B cells, respectively. Four hours after injection of ⁵¹Cr-labeled T and B cells, a large proportion of both cell classes were found in the spleen. By 24 hr, many T cells had left the spleen and appeared in the lymph nodes. Such redistribution by B cells, however, was minimal.Intravenously injected T and B cells, labeled with tritiated uridine (³HU), localized specifically in the T and B cell-dependent areas, respectively, of the lymphoid tissues.³HU-labeled T cells were found to recirculate rapidly from blood to lymph. Labeled B cells, in contrast, recirculated only very slowly.     

Fate of H2-activated T lymphocytes in syngeneic hosts: II. Residence in recirculating lymphocyte pool and capacity to migrate to allografts

T.TDL—a purified population of lymph-borne H2-activated T lymphocytes—were transferred to syngeneic mice to examine their capacity to remain in the recirculating lymphocyte pool (RLP). Experiments with cells labelled with ³H-thymidine (³HTdR) or ⁵¹Chromium showed that although a considerable proportion of T.TDL joined the RLP (i.e., were mobilizable through a thoracic duct fistula) for several days after transfer, most of the cells soon left the pool. This applied whether the cells were transferred to normal mice or to “B” mice. Normal thoracic duct lymphocytes, by contrast, joined the RLP for long periods post-transfer.Studies with ³HTdR-labelled T.TDL showed that a small number of heavily labelled cells remained in the RLP for at least 3 months. Experiments with the θ-antigen as a cell marker suggested that a further small proportion of cells underwent division at some stage after transfer and then rejoined the RLP in expanded numbers.T.TDL showed a tendency to home to specific allografts of either skin, tumor cells or lymphoid cells. Although homing was specific it was very limited in extent.     

Interaction of thymus lymphocytes with histoincompatible cells. IV. Mixed lymphocyte reactions of activated thymus lymphocytes

CS7BL-activated CBA T cells (T.TDL) were obtained by thoracic duct cannulation of (CBA × C57BL)F₁ mice 4 days after heavy irradiation and injection of CBA thymus cells. T.TDL behaved differently from the TDL of normal CBA mice in unidirectional mixed lymphocyte culture in a number of respects: (a) the response of T.TDL was directed specifically against C57BL antigens, whereas normal TDL responded to both C57BL and BALB/c antigens; (b) the response of T.TDL was rapid but transient compared to that of TDL; (c) whereas only approximately 3% of TDL synthesized DNA specifically in response to C57BL antigens, as many as 25% of C57BL-activated T.TDL responded to these antigens. Evidence is presented which suggests that the T.TDL have a very limited capacity to proliferate. Most of the cells which responded to antigen synthesized DNA without subsequently entering mitosis.     

Fate of H2-activated T lymphocytes in syngeneic hosts. III. Differentiation into long-lived recirculating memory cells.

Memory to H2 determinants was studied with an adoptive transfer system using a population of H2-activated blast T cells (T.TDL) obtained from thoracic duct lymph of irradiated F₁ hybrid mice injected with parental strain T cells. CBA T.TDL activated either to DBA/2 or C57BL determinants were transferred to syngeneic “B” mice. Thoracic duct lymphocytes (TDL) were obtained from the recipients 4–6 weeks later and tested for their capacity to produce (a) a graft-versus-host (GVH) reaction, (b) a mixed lymphocyte reaction (MLR) (measured by an in vivo technique) and (c) allograft rejection (suppression of the growth of allogeneic tumour cells in vivo). Control experiments involved testing the function of TDL obtained from “B” mice preinjected with TDL or no cells.TDL from “B” mice injected with TDL (passaged TDL) gave strong MLR and GVH reactions to both DBA/2 and C57BL determinants. Passaged T.TDL activated to C57BL antigens gave intermediate MLR and GVH reactions to the specific (C57BL) determinants but only very low responses to third-party (DBA/2) determinants; reciprocal results were obtained with passaged T.TDL activated to DBA/2 determinants. TDL from “B” mice given no cells failed to respond to either set of determinants.Since the responses by the passaged T.TDL did not exceed those by passaged TDL there was no evidence that adoptive transfer of T.TDL had conferred to the recipients a state of memory to either MLR or GVH determinants. Adoptive transfer did, however, lead to qualitative changes in the properties of T.TDL since, before transfer, they were unable to evoke GVH reactions or produce an MLR of normal kinetics.Passaged T.TDL were far superior to passaged TDL at suppressing the growth of allogeneic tumour cells. The protection was specific since protection against DBA/2 tumour cells was, cell for cell, 5–10 fold more effective with passaged T.TDL activated to DBA/2 determinants than with cells activated to C57BL determinants. No protection was observed with cells treated with anti-θ serum. The protective cells appeared to be precursors of effector cells rather than effector cells per se since they failed to lyse the tumour cells in vitro. These data suggest therefore that the descendants of T.TDL which survived after transfer to “B” mice were highly enriched in long-lived recirculating T lymphocytes reactive to determinants expressed by specific tumour allografts.     

Characterization of recirculating lymphocytes in rheumatoid arthritis patients: selective deficiency of natural killer cells in thoracic duct lymph

Five patients with rheumatoid arthritis (RA), who were treated by lymphocyte depletion by using thoracic duct drainage (TDD), provided an opportunity to characterize the phenotype and function of their recirculating lymphocytes. We found that: a) thoracic duct lymphocytes (TDL) were similar in their proportion of T cells (83% +/- 6 OKT3+), OKT4+ subset (65% +/- 8), and OKT8+ subset (22% +/- 6) to peripheral blood lymphocytes (PBL): b) fewer natural killer-like cells were present in TDL (5% +/- 4 Leu-7+; 2% +/- 2 Leu-11+: 8% +/- 2 OKM -1+) than in PBL (20% +/- 10 Leu-7+: 11% +/- 6 Leu-11+; 18% +/- 5 OKM -1) (p less than 0.01); c) TDL differed from synovial fluid lymphocytes ( SFL ) and synovial membrane lymphocytes ( SML ) in that TDL lacked a high percentage of activated lymphocytes (T cells bearing Ia antigen, OKT10 , and transferrin receptor): d) immature T cells (expressing either OKT6 antigen or reactive with peanut agglutinin) were not found in TDL even late in the course of TDD: and e) in vitro functional studies demonstrated that TDL were similar to PBL in their ability to synthesize immunoglobulin after mitogen stimulation and to generate cytotoxic T lymphocytes capable of lysing autologous EBV-transformed B cells. However, natural killer activity, as measured by lysis of K562 cells was significantly lower in TDL than PBL (p less than 0.05). These results demonstrate that natural killer cells defined by phenotype and function are excluded from thoracic duct lymph and thus have a circulation pattern different from most T cells.     

Fate of H2-activated T lymphocytes in syngeneic hosts. I. Fate in lymphoid tissues and intestines traced with 3H-thymidine, 125I-deoxyuridine and 51chromium.

Information was sought on the fate of T cells activated to H2 determinants in vivo. The cells were obtained from thoracic duct lymph of irradiated F₁ mice injected with parental strain T cells. The fate of the lymph-borne cells—nearly all of which were donor-cell-derived, host-reactive T blasts (T.TDL)—was studied by labelling the cells with either ³HTdR, ¹²⁵IUdR or ⁵¹Cr and transferring them to syngeneic mice.A large proportion of T.TDL (20%) homed to the intestines on transfer. In the small intestine 40% of the cells were located in Peyer's patches; this was lower than with normal TDL (>70%) but higher than with a population of B (θ-negative) blasts (<10%). Some T.TDL were situated within the surface epithelium of the gut. Studies with ⁵¹Cr-labelled cells suggested that a proportion of these cells entered the gut lumen.T.TDL also homed to the large intestine but only when derived from a small inoculum of T cells. T.TDL derived from a large dose of T cells homed preferentially to the small intestine; in this respect they resembled B blasts.Homing to the intestines seemed a general property of T cells activated to transplantation antigens. It was observed irrespective of whether the T.TDL were activated against H2 determinants, M-locus determinants or H2-plus M-locus determinants.Most T.TDL died in the lymphoid tissues within 1–2 weeks of transfer. This conclusion was derived from comparative studies of (a) autoradiographs prepared from recipients of ³HTdR-labelled T.TDL and TDL and (b) the migratory properties of labelled cells harvested from recipients of ⁵¹Cr-labelled T.TDL, normal TDL and irradiated TDL. Rapid clearance of radioactivity from recipients of T.TDL labelled with ¹²⁵IUdR was consistent with this conclusion. Adequate control experiments with this isotope were not possible, however, because attempts to label long-lived lymphocytes (TDL) with ¹²⁵IUdR were unsuccessful.Studies with a variety of cells labelled with ¹²⁵IUdR indicated that a proportion of the label was excreted via the stomach. In certain situations, e.g., in mice with tied renal vessels, extremely high counts (>40% of the injected counts) appeared in the stomach contents.     

Reaction of human lymphocytes with aggregated IgG columns. Effect on antibody-dependent cytotoxicity and EAC rosette formation.

The origin and life span of long-lived small lymphocytes in the bone marrow of mice have been evaluated by the use of radioautography, scintillation counting, and anti-theta serum. Thymus-deprived BALB/C mice and nude mice had a smaller percentage of long-lived lymphocytes in bone marrow and in thoracic duct lymph than sham-operated or normal littermates. Furthermore, the long-lived lymphocytes in the marrow of nudes have more varied—but generally shorter—life spans than long-lived lymphocytes from mice having a thymus. In thoracic duct lymph of nude mice a more homogeneous long-lived population—according to life span—was found.It was concluded that both long-lived T cells and long-lived B cells are normal residents in the bone marrow. Furthermore, it was concluded that cells of variable life spans comprise the B lymphocyte population: short-lived cells with life spans of 3–5 days and long-lived lymphocytes with life spans of weeks to months.     

Migration of recently divided B and T lymphocytes to peritoneum and lung

It is recognized that a population of newly divided (or young) cells migrate preferentially to inflamed foci. It has been shown that a large proportion of lymphocytes residing in the bronchoalveolar airspaces of rat are recently divided cells and that blood may be an important source of these cells. To further delineate how blood may contribute to lymphocyte subpopulations in inflamed peritoneum and lung, a comparison of the capacity of recently divided T and B cells to migrate from blood to inflamed peritoneum and lung was made. To label young lymphocytes, DA strain donor rats were given Initiated thymidine by vein in vivo for 7 days. After thoracic duct drainage, the following labeled cell populations were adoptively transferred by vein into syngeneic recipients: (i) unseparated thoracic duct lymphocytes (TDL), (ii) enriched T cells (>90%) or B cells (>80%) recovered after passage of TDL through nylon columns, and (iii) thoracic duct lymphocytes (> 99% B cells) obtained from “B rats” that were prepared by X irradiation, thymectomy, and bone marrow reconstitution. T and B cells were identified by specific heterologous antisera. The percentage recovery of labeled lymphocytes in the recipients with inflamed peritoneum or lung aspirates was determined from cell counts and autoradiographs. The studies indicated that (a) both labeled T and B cells migrated to inflamed peritoneum and lung; (b) labeled B cells migrated to peritoneum and lung better than did labeled TDL or T cells; and (c) labeled lymphocytes did not migrate to unstimulated peritoneum. The enhanced migration of newly divided B lymphocytes to inflamed peritoneum and normal lung (a site that is likely under chronic antigenic stimulation) was unexpected, but may provide additional information on the relative contribution of these subpopulations in the immune inflammatory response.     

Differentiation of lymphocytes in mouse bone marrow. I. Quantitative radioautographic studies of antiglobulin binding by lymphocytes in bone marrow and lymphoid tissues

The density of surface immunoglobulin on small lymphocytes in the bone marrow and other lymphoid tissues has been compared by radioautographic measurements of antiglobulin binding.Cell suspensions from CBA mice were exposed to ¹²⁵I-labeled rabbit anti-mouse globulin in a wide range of concentrations for 30 min at 0 °C. With increasing concentration of antiglobulin-¹²⁵I the percentage of labeled antiglobulin-binding small lymphocytes in spleen and lymph node suspensions reached well-defined plateau levels. Very few normal or cortisone-resistant thymus cells were labeled under identical conditions. Bone marrow small lymphocytes showed a linear increment in labeled cells throughout the antiglobulin-¹²⁵I dose range, their labeling intensity varied widely, and approximately one half remained unlabeled at high antiglobulin-¹²⁵I concentrations. In 6 wk-old congenitally athymic mice the bone marrow small lymphocyte labeling pattern resembled that in CBA mice, while nearly all (91–97%) small lymphocytes in lymph nodes, thoracic duct lymph and blood, and 75% of those in the spleen, became labeled under plateau conditions. Treatment of cells from 10 wk-old CBA mice with AKR anti-θ C3H serum and complement resulted in almost complete (93%) antiglobulin-labeling of residual small lymphocytes from the spleen but had little effect on bone marrow lymphocyte labeling. Under germfree conditions the proportion of antiglobulin-binding small lymphocytes was slightly elevated in all lymphoid tissues of CBA mice.The results demonstrate that many of the small lymphocytes in mouse bone marrow have readily detectable surface immunoglobulin molecules which vary considerably in density from cell to cell, while others neither have detectable surface immunoglobulin, nor are they θ-bearing, thymus-dependent or recirculating cells. The concept of bone marrow small lymphocytes as a maturing cell population is discussed.     

Vitamin B6 deficiency and the lymphoid system. II. Effects of vitamin B6 deficiency in utero on the immunological competence of the offspring.

Results of this study indicated that an absence of vitamin B₆ from the diet of pregnant rats led to reduced immunological competence in the offspring. While the numbers of cells in the thoracic duct lymph (TDL) of rats approximately 3 months old and progeny of vitamin B₆-deficient mothers were nearly equivalent to control values, such cells had a reduced capacity to respond in the mixed lymphocyte and normal lymphocyte transfer reactions. It is suggested that this reduction may have reflected (i) an alteration in the capacity of TDL cells or their precursors to give rise to immunologically competent cells, (ii) a shift in the proportions of T and B cells in the TDL, and/or (iii) an absence or ineffectiveness of a humoral factor required for the development of immunologically competent lymphocytes.     

Restoration of allograft responsiveness in B rats: IV. The divergent migratory behavior of lymphocyte populations mediating cardiac allograft rejection

The T lymphocyte-deprived (B) rat, produced by X-radiation and bone marrow reconstitution of adolescent thymectomized animals, exhibits a true immunological deficit and are unable to reject histoincompatible heterotopic cardiac allografts. A comprehensive survey of lymphocyte traffic in B recipients was performed to correlate the differential potency of specifically sensitized lymphocyte populations mediating re-establishment of immune responsiveness toward the graft, with their migratory and recirculatory behavior. ¹¹¹In-oxine-labeled thoracic duct lymphocytes (TDL) were retained in the peripheral blood and migrated from nonlymphoid organs to lymph nodes of B recipients in higher proportion than any other lymphoid population, particularly splenic lymphocytes (SL). Although all cell groups but TDL were sequestered in the spleen in equal and relatively large numbers, no differences were found between the lymphocyte populations tested in their capacity to accumulate in the grafts. In contrast, an increased avidity in the allograft of ¹²⁵IUdR-labeled TDL and lymph node (LNL) lymphoblasts, as compared to ¹²⁵IUdR-labeled SL, resembles closely the results of functional studies of the differential potency of adoptively transferred cells. We assume that specific cellular interactions induced by the accumulated ¹²⁵IUdR-labeled cells invoke nonspecific mechanisms for the recruitment of other uncommitted ¹¹¹Inlabeled lymphocytes which recirculate between blood and lymph and localize indiscriminately in the allograft amplifying its rejection. The latter lymphocytes can be “armed” by adherent cells residing in the lymphoid organs of graft recipients, particularly spleen, and subsequently increase the penetration of the foreign tissue. When radiolabeled lymphocytes were traced in B recipients experiencing rejection of their allografts following transfer of sensitized cells plus lymphokine, their migration patterns as well as blastogenic response in B hosts were similar to those observed during acute rejection of cardiac allografts in unmodified hosts. Thus the similarities between the rejection network brought by alloimmune cells into otherwise unresponsive animals and immunocompetent animals able to reject their grafts are stressed.     

Vitamin B6 deficiency and the lymphoid system: I. Effects on cellular immunity and in vitro incorporation of 3H-uridine by small lymphocytes

Thoracic duct lymphocytes from vitamin B₆-deficient rats were found to have a reduced capacity to respond to foreign lymphoid cells in the mixed lymphocyte reaction (MLR), to produce normal lymphocyte transfer reactions, and to incorporate ³H-uridine in vitro. These findings indicate that specific nutritional deficiencies may impair cellular immunity and that this impairment can be monitored by the MLR. It is suggested that the reduction in MLR activity and in ³H-uridine uptake by TDL cells reflected either a shift in the proportions of T and B cells in the TDL and/or an impairment in the capacity of such cells to function in the MLR and in the in vitro test for ³H-uridine incorporation.     

Natural killer cell activity in the rat. V. The circulation patterns and tissue localization of peripheral blood large granular lymphocytes (LGL)

Large granular lymphocytes (LGL) and T cells were separated from blood by centrifugation on discontinuous gradients of Percoll, were labeled with [3H]uridine or [111In]oxine, and were injected i.v. into syngeneic euthymic or athymic nude rats. The tissue distribution of these labeled cells was monitored for up to 24 hr after transfer by scintillation counting of tissue homogenates and autoradiography of tissue sections. In normal euthymic rats, the main sites of LGL localization were the alveolar walls of the lungs and spleen red pulp; however, they were not detectable in the major traffic areas of T lymphocyte recirculation, the spleen white pulp, and lymph nodes. Furthermore, the density of labeled LGL was very low in the small intestine, thymus, kidney, and liver, although on a per-organ basis, about 10% of the injected radioactivity was found in the liver by 24 hr post-injection. When 111In-labeled LGL were injected i.v. into rats with an indwelling thoracic duct cannula, they completely failed to enter the thoracic duct lymphocyte (TDL) population over an observation period of 6 days. This finding was markedly different from the results obtained with T cells and was consistent with the lack of natural killer and antibody-dependent cellular cytotoxicity activity observed among TDL, even in rats pretreated with the biological response modifier, poly I:C. LGL in athymic nude rats also failed to recirculate between blood and lymph. However, in contrast to normal euthymic animals, a significant increase in the localization of radiolabeled LGL to lymph nodes was observed in nude rats between 30 min and 24 hr. Taken as a whole, these findings define the areas within the lungs and spleen in which blood LGL normally localize, and clearly demonstrate that LGL do not normally recirculate between blood and lymph.     

The stable and permanent expansion of functional T lymphocytes in athymic nude rats after a single injection of mature T cells

Athymic nude rats (PVG.rnu/rnu) were injected at 6 to 10 wk of age with 1 to 200 million thoracic duct lymphocytes (TDL) containing 40 to 60% mature T cells. Thereafter TDL-injected nude recipients were monitored for evidence of T cell function for up to 2 yr. W3/25+ T helper (Th) cells in lymph nodes (LN) increased from 7% at 2 wk to 30% at 8 wk after TDL transfer. The percent of W3/25+ cells remained elevated for the life of the recipient (up to 2 yr), approximating normal levels. The total size of the recirculating pool expanded in TDL-injected nude rats to reach 2/3 the level of euthymic controls by 16 wk, an increase of 10-fold to 15-fold in W3/25+ cells. The expansion of the W3/25+ population was independent of initial TDL dose. With time spleen and LN acquired a normal histological appearance including the development of germinal centres and a marked increase in cellularity in T cell traffic areas. TDL-injected nude rats rejected skin allografts with near normal kinetics. In addition graft vs host (GVH) responsiveness, assessed by the popliteal LN assay, progressively increased reaching a level 9 mo to 1 yr after replacement that resembled the GVH activity in euthymic controls.     

Biophysical characterization of peyer’s patch lymphocytes in the B-cell deficient CBA/N mice and in their F1 hybrids

CBA/N mice bear an X-linked immunodeficiency involving abnormalities of their B lymphocytes. We investigated the electrophoretic mobility (EPM) distribution and the electronic volume of the Peyer's patch (PP) cells of these mice in comparison with those of the immunologically normal CBA/J mice. The same studies were also carried out on PP cells from the CBA/N×DBA/2 (CND2) F1 hybrid males and females that are, respectively, B-cell defective and normal. In all types of mice, PP cells could be separated by free-flow electrophoresis into a low-mobility (LM) population corresponding mainly to B cells and high-mobility (HM) population containing mostly T cells. However, while in the control mice LM (B) cells accounted for around 60–67% of PP lymphocytes, this population did not exceed 40% in the defective animals. Furthermore, LM (B) cells, but not HM (T) cells, of CBA/N and CND2 male mice were found to display abnormal physical characteristics. Thus, they possessed a higher anodic EPM (two electrophoretic fractions faster) and a slightly larger model size (134 μm³) than normal adult B cells (122–124 μm³). Similar differences were observed with PP lymphocyte preparations enriched for B cells by nylon wool adherence. These data suggest that CBA/N mice and their defective hybrids lack a population of small B lymphocytes with low anodic EPM.     

Adoptive transfer of the intestinal mast cell response in rats infected with Nippostrongylus brasiliensis.

The intestinal mast cells (IMC) were examined in normal and adoptively immunized rats infected with Nippostrongylus brasiliensis. An increase in the numbers of IMC was observed in infected recipients of thoracic duct lymphocytes (TDL) obtained from donor rats which had themselves been infected 10 days previously (Day 10 TDL). The increase in the number of IMC in the mucosa was related to the number of Day 10 TDL transferred into infected recipients. When TDL were fractionated into populations of cells either bearing (sIg⁺) or lacking (sIg^?) surface immunoglobulin, only sIg^? cells were able to confer the IMC response. Antigenic stimulation was necessary for the differentiation of intestinal mast cells. There was a marked difference between different strains of rats with regard to worm burden and intestinal mast cell kinetics although the increase in intestinal mast cells was always closely related to the final stage of the rapid phase of worm expulsion. These results are compatible with the concept that intestinal mast cells are derived from T cells and suggest that sIg⁺ cells do not influence IMC differentiation. Alternatively, the possibility that the transferred TDL regulate the differentiation of cells of host origin into IMC cannot be excluded.     

LYSOSOMES IN RAT THORACIC DUCT LYMPHOCYTES FRACTIONATED BY ZONAL CENTRIFUGATION

A method of zonal centrifugation was developed which separates rat thoracic duct lymphocytes (TDL) mainly according to size. The validity of the fractionation method was supported by light microscope observations, Coulter Counter sizing, and in vivo and in vitro labeling of lymphocytes. The distributions of lysosomal acid hydrolases in TDL fractionated by zonal centrifugation are similar to the distribution obtained for the cells. This result indicates that the large lymphocyte is not the sole bearer of either lysosomes or the large amount of soluble cathepsin D found in homogenates of TDL. Both reside mainly in small lymphocytes. This point was clearly established by fractionating homogenates of purified small lymphocytes by means of differential centrifugation and isopycnic density gradient centrifugation.     

Radiosensitivity of T and B lymphocytes. IV. Effect of whole body irradiation upon various lymphoid tissues and numbers of recirculating lymphocytes.

Groups of 10-week-old female CBA/J mice were exposed in whole body fashion to 0,5,50, and 500 rads and sacrificed in serial fashion 1,3,5,7,9,15, and 30 days after irradiation for morphologic evaluation of thymus, spleen, lymph node, and Peyer's patch, and assessment of the relative numbers of thymus-derived (T) and bone marrow-derived (B) cells in these tissues. The absolute and relative numbers of recirculating T and B cells mobilizable by thoracic duct cannulation were also determined and compared with similar determinations with respect to peripheral blood lymphocytes. B cell depletion occurred more quickly and was more pronounced in spleen and lymph node than T cell depletion at all three exposure doses. Depletion of T and B cells was roughly equal in peripheral blood and thoracic duct lymph. When present, regeneration of the T cell component occurred more rapidly than did B cell restoration. The latter often was incomplete at the time of the final sacrifice (day 30). PHA-responsive and Con A-responsive cells also appeared to differ with respect to the kinetics of cell death after whole body irradiation.     

Detection of the precursor and effector cells of experimental allergic encephalomyelitis in the thoracic duct of the rat

Despite strong evidence pointing to the fundamental role of the T cell in the pathogenesis of experimental allergic encephalomyelitis (EAE), little has been known about the normal traffic of the precursor (unprimed) and effector (primed) cells of EAE. We have demonstrated the recirculation of the precursor cells in that B rats regained their susceptibility to EAE following reconstitution with thoracic duct lymphocytes (TDL) passed through an irradiated intermediate host as well as following reconstitution with normal thymocytes or normal TDL. The effector cells were shown to be present in TDL in that TDL from donors immunized 11 or 12 days prior to transfer could passively transfer EAE to naive recipients.