Effect Of Adult Thymectomy Research Articles

The Effect of Adult Thymectomy on Immune Response to Infection with Listeria monocytogenes in Mice

The role of adult thymus in in vivo immune response to infection with Listeria monocytogenes was examined using euthymic mice and adult-thymectomized (ATx) mice which had been thymectomized 2 weeks before. Numbers of T cells in peritoneal cavities and spleens were increased at 2 weeks after inoculation of L. monocytogenes, whereas such increases of T cells were several times higher in euthymic mice than in ATx mice. In flow-cytometric analysis of peritoneal exudate cells, a significant increase of CD3 +CD4 −CD8 − cells bearing γ/δ type T cell receptor was noted in euthymic mouse after infection compared to ATx mouse. Neither assay of antigen-specific T cell proliferation nor analysis of cell cycle exhibited any superiority of T cells obtained from euthymic mice to those obtained from ATx mice. These findings suggest that the enlargement of T cell population in euthymic mice is attributed largely to T cells which emigrate from the thymus after inoculation of L. monocytogenes. Moreover, in vivo protective immune response against secondarily challenged L. monocytogenes was achieved more efficiently in euthymic mice than in ATx mice, as shown by the clearance of the bacteria from organs and the survival rate of infected mice. Our results indicate the importance of adult thymus-dependent increase of T cells in eliminating the facultative intracellular bacteria such as L. monocytogenes.

The effect of adult thymectomy, cyclophosphamide treatment and gamma irradiation on the NOD/Wehi mouse

The effect of adult thymectomy, cyclophosphamide treatment and gamma irradiation on the NOD/Wehi mouse

Temporal changes of suppressor T lymphocytes and cytotoxic T lymphocytes in syngeneic murine malignant gliomas.

The temporal activities of suppressor T lymphocytes (Ts) and cytotoxic T lymphocytes (CTL) were investigated in a syngeneic murine malignant glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin, 203-glioma). After the s.c. tumor inoculation, it was suggested that both Ts and CTL were generated with target specificity against 203-glioma cells, because neither Ts nor CTL activity were seen against syngeneic EL 4 (benzpyrene-induced thymoma), allogeneic P815 (methylcholanthrene-induced mastocytoma of DBA/2 mouse origin) or YAC-1 (Moloney leukemia-induced T-cell lymphoma of A/Sn mouse origin), but only against 203-glioma. It was found that the generation of Ts preceded that of CTL and that the turnover was faster; furthermore, Ts were generated in the thymus and spleen, while CTL were distributed in regional lymph nodes and spleen. Surface marker analysis revealed that only Lyt-1-.2.3+ T-cells participated in suppressor responses in contrast to both Lyt-1-.2.3+ and Lyt-1+.2.3+ T-cells participating in cytotoxic responses. The effects of adult thymectomy (ATx) on the changes of the immunized T-cell subsets were also investigated. In mice thymectomized 3 weeks previously, the Ts activity was abrogated, whereas the CTL activity increased markedly and Lyt-1+.2.3+ T-cells were not detected. The results suggest that CTL or their precursors bearing Lyt-1+.2.3+ phenotype and Ts bearing Lyt-1-.2.3+ phenotype are short-lived lymphocytes. Accordingly, it is suggested that in tumor-bearing mice short-lived Ts are generated earliest with target specificity and, due to the reciprocal relationships between Ts and CTL activities, may have a modulating influence on CTL; furthermore, ATx may alter the patterns of generation of the precursor T-cells and Ts.

Fluid and mononuclear cells from healing wounds inhibit thymocyte immune responsiveness

It has been shown previously that fluid obtained from 7-day-old wounds noncytotoxically inhibits normal thymic lymphocyte blastogenesis and that mononuclear cells (MNC) from the same wounds lack mitogenic responsiveness. The present series of experiments studies whether wound MNC are the source of the wound inhibitory factor(s) and the effect of adult thymectomy (ATDX) on their generation. Adult male Sprague-Dawley rats (300–350 g), intact or ATDX (performed at 8–10 weeks of age), underwent dorsal wounding (7 cm) and subcutaneous implantation of sterile Ivalon sponges. Seven days later sponges were harvested, wound fluid was obtained, and the cell pellet was purified to 90% MNC. Normal rat thymocyte blastogenesis (stimulation index) to Con A and PHA evaluated in a microculture system (10 separate experiments) was 169.9 ± 10.0 and 30.1 ± 3.7. Addition of 10% wound fluid markedly inhibited thymocyte mitogenesis—6.3 ± 1.0 and 2.7 ± 0.6, respectively ( P < 0.001). Heat-inactivated wound fluid (56°C, 30 min) had similar inhibitory activity—3.4 ± 0.9 and 2.7 ± 0.6 ( P < 0.001). Normal thymic blastogenesis could also be inhibited by the addition of 5 × 10 4 wound MNC to the microculture system—4.4 ± 1.1 and 1.9 ± 0.3 ( P < 0.001). Wound fluid from ATDX rats had much less inhibitory activity (77.1 ± 22.4 and 7.2 ± 2.1, P < 0.01) vs control wound fluid. In addition wound MNC from ADTX animals were also less immune suppressive (30.7 ± 4.9 and 13.5 ± 3.7, P < 0.001) than control MNC. Forty-eight-hour supernatants of wound MNC from intact rats, added in 25% concentration to normal thymocyte cultures, demonstrated inhibition similar to that of the wound fluid from the same animals: 4.4 ± 0.7 and 3.9 ± 0.6, while ATDX MNC supernatants had minimal inhibitory activity (110.1 ± 18.2 and 25.7 ± 6.5, P < 0.005). No cytotoxicity could be demonstrated in any of these experiments by trypan blue exclusion. It is concluded that 7-day-old wound fluid noncytotoxically inhibits thymocyte blastogenesis; this effect is also demonstrated by wound MNC and their supernatants, suggesting immune “suppressor” lymphocytes are present in wounds; ATDX, which abrogates suppressor cell induction, leads to marked diminution of wound inhibitory activity. The data suggest that important immune events occur at the wound site; their relation to normal wound healing remains to be elucidated.

Effect of adult thymectomy and splenectomy on pluripotent stem cells and progenitors of the myeloid and B-lymphoid lineages

In order to investigate the regulatory interactions which occur between the bone marrow, the thymus and the spleen during hemopoiesis, the numbers of granulo-macrophage and B-lymphocyte precursors (GM-CFC and BL-CFC) and the kinetics of pluripotent stem cells (CFU-S) have been studied in the bone marrow and the spleen of normal adult thymectomized and/or adult splenectomized mice with or without T-dependent antigen stimulation. The results suggest that (1) medullary and splenic CFU-S may be two different populations of the stem cell compartment; (2) the thymus is involved in medullary but not in splenic CFU-S proliferation in response to T-antigen challenge; (3) the spleen influences GM-CFC and BL-CFC numbers and (4) antigenic stimulation modifies medullary BL-CFC.

Effect of adult thymectomy on immune potentials, endocrine organs and tumor incidence in long-lived mice.

The data presented here indicate that the thymus plays an important role not only in the early ontogenic development of the immune system, but also in the maintenance of the immune potentials throughout the course of life. Moreover, thymic function is closely interrelated with functions of the other endocrine organs.

Effect of adult thymectomy on the development of 1-chloro-2,4-dinitrobenzene contact sensitivity and other T lymphocyte functions in patients with myasthenia gravis.

1-Chloro-2,4-dinitrobenzene (DNCB) contact sensitivity and other T lymphocyte functions were studied in thymectomized and non-thymectomized patients with myasthenia gravis. The ability to develop contact sensitivity was reduced in patients with myasthenia gravis and was further reduced after thymectomy. Memory lymphocyte function, as measured by skin tests with common microbial antigens, was intact. A positive phytohemagglutinin (PHA) skin test was found mainly in those patients who also developed contact sensitivity to DNCB. The number of rosette-forming T cells in the peripheral blood as well as mitogen stimulation with PHA was found to be normal in thymectomized as well as non-thymectomized patients. In the thymectomized group, mitogen stimulation with concanavalin A and staphylococcal protein A was also within the normal range, while increased stimulation was obtained with pokeweed mitogen (PWM) and purified protein derivative (PPD). No alteration in mixed lymphocyte culture reactivity or immunoglobulin levels was obtained compared with healthy blood donors. On the basis of these results, it is concluded that non-thymectomized as well as thymectomized patients with myasthenia gravis may have a defective subpopulation of T cells possibly residing in the TH1-positive population. Furthermore, the increased lymphocyte stimulation obtained with PPD and PWM may indicate a reduction of suppressor cell activity after thymectomy.

Regulation of Contact Sensitivity to Dnfb in the Mouse: Effects of Adult Thymectomy and Thymic Factor

The contact sensitivity response to DNFB is decreased after adult thymectomy (ATX). This response decreases to 50% of the control response of normal age-matched mice as soon as 3 weeks after ATX and is not further depressed 9 to 16 weeks after ATX. These results suggest that two T cell subsets of different lifespan are involved in the anti-DNFB response. A circulating thymic factor (FTS) is able to restore the contact sensitivity response to DNFB when injected 3 to 9 weeks after ATX but not 16 weeks later. By contrast, FTS has a depressive effect on the contact sensitivity response to DNFB of normal mice through a cyclophosphamide-sensitive T cell subset. These results suggest that FTS regulates DNFB contact sensitivity by acting on a cyclophosphamide-sensitive T cell subset, still present 9 weeks after ATX but absent after 16 weeks. Thus although the T cell defect, causing a depression of the contact sensitivity reaction to DNFB is quantitatively similar 3 and 16 weeks after ATX, its nature is probably different.

The nature of the thymus dependency of mucosal mast cells: II. The effect of thymectomy and of depleting recirculating lymphocytes on the response to Nippostrongylus brasiliensis

The effect of adult thymectomy and of lymphocyte depletion by thoracic duct drainage on the jejeunal mucosal mast cell (MMC) response to infestation with Nippostrongylus brasiliensis has been studied in rats. Adult thymectomy 2 to 4 weeks before infestation with the parasite had no effect on the production of MMC hyperplasia. However, long-term thymectomy (12–39 weeks) produced a progressive decline in the MMC response to infestation. When adult-thymectomized rats were depleted of recirculating lymphocytes by thoracic duct drainage, infestation either 2 weeks or 12 weeks after completion of drainage significantly reduced the MMC response. The MMC response was restored to normal when the animal's washed thoracic duct lymphocytes were returned to it, and could be regenerated over the course of 12 weeks in the presence of thymus tissue. It is concluded that the thymus influences MMC indirectly, through the production of peripheral T lymphocytes, and that the T-lymphocyte subset involved belongs to the long-lived recirculating pool.

Modulation of Age-related Development of Contact Sensitivity in Mice by Adult Thymectomy

The effect of adult thymectomy on antibody production and on the development of contact sensitivity to picryl chloride in mice of different ages was studied. An age-dependent decline in the ability to develop contact sensitivity was found to be counteracted by thymectomy. In contrast, antibody production was regularly decreased by thymectomy in mice of all ages. A hypothesis is put forward in which the development of contact sensitivity may be regulated by long-lived thymus-dependent suppressor cells which do not affect antibody formation.

Effect of adult thymectomy on tumour immunity in mice

The effect of adult thymectomy in DBA/2J mice on the in vitro response to syngeneic tumour cells was investigated. Spleen cells from adult mice which had been thymectomized 8 weeks previously demonstrated a severely impaired primary cytotoxic response to P815 tumour cells, whereas their cytotoxic responses to allogeneic cells (C57BL/6) and to non-H-2 antigens (BALB/c), and their ability to form a primary antibody response to sheep red blood cells was unimpaired. Suppressor T cells, specific for P815 cells, appeared early in the thymuses of animals inoculated with P815 cells (between 4 and 8 days after tumour-cell injection). No differences in tumour growth between animals thymectomized as adults and sham-operated controls were observed, and thymectomized tumour-bearing animals had levels of specific suppressor cells in their lymph nodes equivalent to the levels found in untreated controls. Severely thymocyte-deprived animals which had been thymectomized, irradiated and reconstituted with either marrow or spleen cells 8 weeks before tumour implantation succumbed more rapidly to metastatic tumour than did control animals.

Identification of T cell subpopulations binding phytohemagglutinin: functional characteristics.

AbstractLymphocytes binding 125I‐labeled phytohemagglutinin (125I‐PHA) were directly quantitated by autoradiography. The distribution of grain counts proved to be trimodal indicating the presence of three distinct subpopulations of PHA‐binding cells. Low intensity binders (median grain count of 8–12 grains/cell) predominated in spleen and lymph node, included B and T cells, and responded to the mitogen, lipopolysaccharide (LPS). High intensity binders (median grain count greater than 60 grains/cell) occurred at low frequency in every lymphoid organ, were T cells, and included mixed lymphocyte culture (MLC)‐reactive but not PHA‐reactive cells as judged by preferential sensitivity to suicide with 125I‐PHA. Medium intensity binders (median grain count of 40–45 grains/cell) predominated in the thymus, formed a subpopulation in the spleen and lymph nodes of normal mice, but were absent from bone marrow of normal mice and the spleen of nude mice. In addition, their numbers were markedly reduced following adult thymectomy and cortisone treatment indicating that they were most likely T cells of recent thymic origin.PHA‐reactive cells were considered to belong to the medium intensity PHA‐binding subpopulation. This conclusion was based on the following: first, medium intensity binders, like PHA‐reactive cells, were T cells; second, they were contained in the same subpopulation of T cells as PHA‐reactive cells. That is, they were of recent thymic origin (T1 cells) according to studies of tissue distribution, cortisone sensitivity and effect of adult thymectomy; third, “suicide” of the response to PHA as well as to allogeneic cells but not LPS was achieved by prior incubation of cells with high doses of soluble 125I‐PHA, whereas lower doses resulted only in abrogation of the MLC response. In other words, PHA‐reactive cells resided in the medium, rather than high intensity subpopulation of binding cells. By analogy with suicide of antigen‐binding cells, this observation implies that PHA binds preferentially to those cells responding to it, and confirms the validity of using mitogen activation as a model for antigen‐induced triggering. On the other hand, binding of PHA to a subpopulation of T cells casts doubt on the value of the PHA response as a measure of overall T Cell function. Support for this conclusion came from the failure of PHA suicide to abrogate effector T cell activities such as help and suppression.

Role of T Lymphocytes in Adjuvant Arthritis

Abstract The effects of treatments with cyclophosphamide (CY), hydrocortisone and anti-thymocyte sera (ATS) on the development of adjuvant arthritis (AA) were examined in WKA rats inoculated with wax D to induce AA. A single injection of 25 to 50 mg/kg of CY given 2 to 3 days before wax D inoculation caused severe arthritis with high incidence, whereas larger doses of CY were less efficient. Furthermore, the enhancing effect of CY pretreatment was abolished by passively transferred normal syngeneic thymocytes 1 day before wax D inoculation, but not by thymocytes that had been treated with ATS and guinea pig C. On the basis of these results and the previous observations on the effect of adult thymectomy and low-dose irradiation, we concluded that this enhancing effect of CY pretreatment was caused by selective depletion of suppressor T lymphocytes. Pretreatment with 12.5 mg of hydrocortisone also caused severe arthritis. This enhancing effect of hydrocortisone could also be due to the elimination of those suppressor cells. In contrast, in vivo pretreatment with ATS showed striking inhibition on the development of AA, suggesting that ATS could eliminate T lymphocytes that were responsible for eliciting this disease. Thus it appears that at least two T cell subpopulations are involved in the development of AA, one is an ATS-sensitive T2 subpopulation that is effective for induction of AA and the other is a T1 subpopulation that regulates this disease process.

Increased stimulatory capacity of spleen cells from adult thymectomized mice in mixed lymphocyte reactions.

Conflicting results have been reported concerning the effect of adult thymectomy (A-Tx) on the mixed lymphocyte reaction (MLR) response. Our purpose was to test the reverse question, namely the effect of A-Tx on the stimulatory capacity of mouse lymphocytes carrying allelic disparities at the Mls and the H-2 loci. Spleen cells from A-Tx CBA donors were found to be significantly more stimulating than cells from normal donors. That A-Tx could eliminate suppressor T cells involved in MLR regulation or in preventing back stimulation is not likely according to our data. An increment in expression or in accessibility of Mls or H-2 antigenic determinants induced by A-Tx is no more likely, since a smilar increase in lymphocyte proliferation was observed in syngeneic cultures. The most probable explanation remains that A-Tx discloses a strongly stimulatory subpopulation, perhaps acting in part nonspecifically. The hypothesis of an enrichment in B cells versus a loss of T cells is not compatible with our findings, since B-cell-enriched fractions from various origins never attained the stimulating ability disclosed by A-Tx cells. Moreover, the cell involved is theta-positive, although slightly nylon-wool-adherent, and thus shares several properties with immature T cells involved in auto-rosette formation.

Regulation of the immune response by subclasses of T lymphocytes. II. The effect of adult thymectomy upon humoral and cellular responses in mice.

The immunologic consequences resulting from thymectomy in adult life were investigated. Primary humoral responses were not diminished shortly after adult thymectomy, as judged by responses of intact thymectomized mice as well as by the ability of spleen cells from such mice to transfer primary responses. However, secondary humoral responses were substantially reduced in irradiated recipients of spleen cells from primed adult-thymectomized mice, suggesting that the thymus is required in adult life to maintain a population of cells important in the generation of immunologic helper memory. By contrast, small doses of anti-thymocyte serum, which primarily affect recirulating T cells, abrogated the primary humoral response, but allowed the subsequent development of immune memory. Using a technique permitting in vitro sensitization of purified T cells to alloantigens, it was shown that adult thymectomy increases the ability of T cells to generate primary cytotoxic responses, but had little effect upon the development of cytotoxic T memory activity. These experiments suggest that in adult life the thymus maintains a regulatory population of T cells in peripheral tissues which suppress early T cell differentiation to cytotoxic effector cells and potentiates the development of immune memory.

Differences in the effects of adult thymectomy on T-cell mediated responses in vitro.

EVIDENCE exists indicating that functionally different subsets of T lymphocytes are activated during the in vitro allograft response. Thus, the T cells responding primarily by proliferation in the mixed lymphocyte culture (MLC) may be distinct from the T cells which differentiate to killer cells and display specific target cell lysis (CML)1–3. The biological properties of the T-cell subsets involved are incompletely known. Adult thymectomy (ATX) in mice and rats alters certain T lymphocyte mediated functions. Spleen T cells forming rosettes with sheep erythrocytes disappear as soon as 5 d after ATX4,5. Lymphocyte with high amounts of surface θ antigen are depleted from the spleen within a few weeks after the operation (Ref. 6 and C. Fournier and J. F. B., unpublished).

The effect of adult thymectomy in dogs on the immunosuppressive activity of antilymphocyte serum (ALS).

AbstractIn the series of our studies on antilymphocyte serum (ALS) as an immunosuppressive agent in transplantation of the canine larynx, the use of ALS in thymectomized dogs was attempted for the purpose of increasing the immunosuppressive effects of ALS.Immunoglobulin G (IgG) was purified by DEAE‐cellulose batch production method from the high titer horse anti‐dog thymocyte plasma (ATP) and low titer ATP, respectively. A skin allograft assay was used to measure the immunosuppressive activity.Adult thymectomy previous to administration of the high titer‐IgG and low titer‐IgG, respectively, did not augment the immunosuppressive effect of these ATP‐IgG's.

Effect of adult thymectomy and antilymphocyte globulin treatment on metastases in an allogeneic mouse tumor system.

Effect of adult thymectomy and antilymphocyte globulin treatment on metastases in an allogeneic mouse tumor system.