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PubMed1982

Loss of tolerance to thymus-donor strain antigens in nude mice bearing long-term allogeneic thymus grafts.

In contrast to lymph node cells from nonthymus gland-implanted nude mice, which failed to respond to foreign alloantigens in mixed lymphocyte reaction tests, lymph node cells from nude mice implanted with either syngeneic or allogeneic thymuses responded well following stimulation with third-party allogeneic cells from strains unrelated to the nude host or thymus-donor strain. Responses to thymus-donor strain alloantigens by lymph node cells from nude mice implanted with allogeneic thymuses were in part dependent upon the duration of the thymic implants; no responses were observed using cells from mice implanted 3 mth previously whereas the majority of experiments yield positive responses using cells from mice implanted 12 mth previously, suggesting a functional breakdown of the tolerant state with time post allogeneic thymus implantation. In no case were positive responses specific for the nude host strain observed.

Animals↗
PubMed1974

Antibody responses to antigenic determinants of influenza virus hemagglutinin. I. Thymus dependence of antibody formation and thymus independence of immunological memory.

Using immunodiffusion methods it has been shown that purified hemagglutinin (HA) extracted from two related strains of influenza A viruses (A/PR8/34 and A/FM1/47) have two distinct antigenic determinants, or groups of determinants. One determinant is cross-reactive while the other is strain-specific. Antisera raised in normal mice against HA were shown to contain two populations of antibody molecules, each directed against one of the determinants. Immunization of thymus-deprived (TXBM) mice showed a strong thymus dependence of antibody formation to HA. However, the thymus dependence of antibody formation against the cross-reactive determinant could be overcome by repeated inoculations of HA in TXBM mice, indicating a different handling of two portions of the same molecule by the immunological system. Strong, secondary-type responses to the strain-specific determinant were observed in primed thymus-deprived mice after reconstitution with virgin thymus cells, showing that specific immunological memory was elicited by this determinant despite the absence of detectable antibody secretion. These findings are interpreted as examples of immunological recognition and memory mediated by B lymphocytes and discussed in terms of mechanisms of T and B lymphocyte co-operation. It is suggested that the helper effect of T lymphocytes is exerted at a late stage in the differentiation of specific populations of B cells into antibody-secreting cells.

Animals↗
PubMed1975

The postnatal development of the white pulp in the rat spleen and the onset of immunocompetence against a thymus-independent and a thymus-dependent antigen.

The spleen of the rat contains 5 well delineated compartments: a central and peripheral part of the periarteriolar lymphatic sheath (PALS), the marginal zone and the follicle with centre and corona. A study was made on the development of these compartments in correlation with the onset of immunocompetence of the spleen. The spleens of animals in the age range from 1-40 days were studied with the light and electron microscopes. Immunocompetence was assessed by measuring serum antibody levels 5 days after intravenous antigen administration. Comparable doses of paratyphoid vaccin (PTV) and sheep red blood cells (SRBC) were used: PTV as a thymus-independent, SRBC as a thymus-dependent antigen. At the first day of life few lymphocytes are present around small arterioles. The marginal zone is first present at 9 days of age. At 14 days of age the typical thymus-dependent area develops. Interdigitating cells, which seem to develop from monocytes, and lymphocytes are present in close apposition. Primary follicles were first seen on 20 days of age, follicle centres at 25 or 30 days of age. The appearance of "typical" dendritic cells coincided with the appearance of follicle centres. The first titre against PTV was seen after antigen administration at 9 days after birth, against SRBC after injection in 14 days old animals. As PTV is a thymus-independent antigen it needs only B-cells for a primary IgM response. The appearance of functional B-cells in sufficient numbers to give a measurable response therefore coincides with the appearance of the marginal zone. Although T-cells are present from birth, the response against SRBC is delayed until the thymus-dependent area has developed. Thus, in the first 2 weeks of life, T-cells are either immature, or they are not able to react, because their microenvironment is not yet adequate.

Animals↗
PubMed1981

Thymus-dependent and thymus-independent antibody responses: contrasting patterns of immunosuppression.

The effects of mitoclomine, an anti-tumour agent, and of cortisone acetate on the antibody response of mice to thymus-dependent and thymus-independent antigens were compared. Both agents yielded patterns of immunosuppression which differed from that seen after X-rays, an agent which is likely to be active equally against T and B cells. Mitoclomine, at low doses, depressed thymus-independent responses the most; this effect can be explained if the drug is more active against B than T cells. Cortisone acetate at low doses, while depressing thymus-dependent responses, increased thymus-independent responses; this can be explained if the drug is more active against T than B cells. Thus three different patterns of immunosuppression (for X-rays, mitoclomine and cortisone acetate) can be interpreted in terms of effects simply on T or B cells.

1-Naphthylamine↗
PubMed1992

Thymus cells in myasthenia gravis: a two-colour flow cytometric analysis of lymphocytes in the thymus and thymoma.

The thymus in patients with myasthenia gravis has germinal centres and the thymic lymphocytes spontaneously produce anti-acetylcholine receptor antibody in vitro. This suggests indirectly that the myasthenic thymus contains mature T and B cells that are autoreactive. We report a two colour flow cytometric analysis of the surface antigen phenotype of lymphocytes in the thymus and in thymoma in 24 patients and in 14 normal thymuses. The results show a decline in the proportion of double positive immature thymocytes with age. This process seems to be partially disrupted in patients with myasthenia gravis. In addition titres of anti-acetylcholine receptor antibody were positively correlated with the proportion of mature single positive T cells and non-T DR positive cells.

Adolescent↗
PubMed1985

Myasthenia gravis: long-term prognostic value of thymus lactate dehydrogenase isoenzyme pattern of hyperplastic thymus and thymoma.

Lactate dehydrogenase (LDH) isoenzyme pattern and the percent of H-subunit content were determined in the thymus of 62 patients (55 with hyperplasia, 7 with tumours) after thymectomy. An increase in LDH1 relative activity indicates that in the thymus of patients with myasthenia gravis the ratio of mature differentiated thymocytes was higher than in the thymus of control subjects. LDH isoenzyme profiles of thymus tumours were similar to those described in other neoplasms, except that thymomas with apparent predominance of epithelial cells and with minimal lymphocytic reaction exhibited a marked elevation only in LDH2 relative activity, presumably associated with the specific (secretory) function of epithelial cells. The elevation of H-subunit content, a parameter characteristic of both thymic components (lymphoid and epithelial), correlated closely with a poor clinical condition in patients several years after surgery.

Adolescent↗
PubMed1984

Contribution of thymus lymphocytes to the peripheral lymphoid tissues and the effect of antigen on the rate of cell exit from the thymus.

Some of the important questions concerning the development of T cells in the thymus can be answered by a study of the different thymocyte subpopulations and a comparison of their properties with those of the cells exported to the peripheral lymphoid tissues. What is the relationship between cortical and medullary thymocytes? Why do most cortical cells die? Which subpopulation gives rise to thymus migrants? How many cells are exported from the thymus? Are the exported cells fully mature? Are any of these functions affected by antigen stimulation or other peripheral events? In this paper we review the background to some of these questions and focus on the effect of peripherally administered antigen on the export of cells from the thymus. Experimental data are presented which suggest that the overall rate of emigration is not grossly affected by large doses of intravenous protein antigens. Nor is there any obvious qualitative change, at least in terms of the size of the cells released. The possibility of changes in the specificity of the exported cells is discussed, but as yet there are no data which throw light on this point.

Animals↗
PubMed1984

Detection and localization by the monoclonal anti-interleukin 2 receptor antibody AMT-13 of IL 2 receptor-bearing cells in the developing thymus of the mouse embryo and in the thymus of cortisone-treated mice.

During embryonic development of the mouse, before expressing classical T cell markers, the blast cells colonizing the thymus react with the monoclonal antibody AMT-13 shown previously to detect interleukin 2 receptors. The proportion of AMT-13+ cells decreases as gestation time increases. On the other hand, the proportion of Thy-1+, Lyt-1+ and Lyt-2+ cells increases during ontogenesis. On the 19th day of gestation when the thymus architecture is comparable to the adult thymus, the AMT-13+ cells become localized in the subcapsular area of the cortex. In the adult thymus after cortison treatment the regenerating cells express the AMT-13 antigen. The AMT-13 antigen presumably the interleukin 2 receptor is the first marker of the early embryonic thymocytes reported until now that may be related to cellular function.

Animals↗
PubMed1989

Detection of antibodies to extractable nuclear antigens using calf thymus and rabbit thymus. A comparative study of 1000 consecutive anti-nuclear antibody positive patients.

A comparison between calf thymus extract and rabbit thymus extract to determine their suitability for clinical laboratories in detecting antibodies to extractable nuclear antigens (ENA) was undertaken. Calf thymus extract (CTE) detected 90% more ENA positive patients and 155% more lines than rabbit thymus extract (RTE). In contrast to RTE, CTE resolved Sm and RNP into two distinct lines, had superior stability at -80 degrees C and produced greater clarity of definition of precipitin lines.

Animals↗
PubMed2005

Alternatively spliced transcripts of the thymus-specific protease PRSS16 are differentially expressed in human thymus.

The putative serine protease PRSS16 is abundantly expressed in the thymic cortex and the gene is encoded within the HLA I complex. Although its function is not yet defined, the very restricted expression points to a role in T-cell development in the thymus. In this study, we show that the PRSS16 mRNA is alternatively spliced to generate at least five transcripts. Apart from the full-length sequence, we found two other isoforms with all putative active site residues of the serine protease, suggesting that those variants may also be functional. Semi-quantitative analysis of the splice variants in different tissue samples revealed a strong correlation between the specific formation of alternatively spliced PRSS16 transcripts and the age and thymus pathology status of the donor. Newborn thymi express mostly the PRSS16-4 and -5 isoforms and lack the PRSS16-1 transcript, which appears around 2 years of age and stays until adulthood. Incidentally, thymi from myasthenia gravis (MG) patients with thymoma showed a marked decrease in the expression of the full-length PRSS16-1 and increased expression of the smaller isoforms. The data suggest a potential role of the PRSS16 isoforms in the postnatal morphogenesis of the thymus and in the thymus pathology related to MG.

Adult↗
PubMed1970

Synergism of thymus and bone marrow in the production of gra a5hilgard HR: Synergism of thymus and bone marrow in the production of graft-versus-host splenomegaly in x-irradiated hosts.

Graft-versus-host splenomegaly may be elicited from 500 R X-irradiated F(1) hybrid hosts if the hosts are injected with bone marrow cells and thymus cells from parental strain donors. Cells from thymus only or bone marrow only will not elicit graft-versus-host splenomegaly in these hosts. In this requirement for cells from both sources, the bone marrow cells play a nonimmunologic, proliferative role in the splenomegaly, and the thymus cells carry out the immunologic attack. Thus the mechanism of this synergism is quite different from that reported for the humoral immune response to sheep erythrocytes in which both thymus and marrow interact in the production of the specific immunologic response itself.

Animals↗
PubMed2004

Effect of honey on antibody production against thymus-dependent and thymus-independent antigens in primary and secondary immune responses.

The objective was to study the effect of natural pure honey on the antibody production against thymus-dependent antigen [sheep red blood cells (SRBCs)] and thymus-independent antigen (Escherichia coli) in mice. Forty-two mice (mean weight 28.33 +/- 3.44 g) were divided into two groups: group A (21 mice) fed regular diet and group B (21 mice) fed regular diet plus 0.8 g/kg of body weight/day of honey administered in four equally divided doses. Each animal was injected intraperitoneally with 0.1 mL of 5% SRBCs and 0.1 mL of killed E. coli. The same dose of both antigens was given after 17 days. At days 7 and 16 after primary immunization and at day 4 after secondary immunization, blood samples were collected from seven mice at each time interval from group A and group B to estimate antibody titer using the hemoaggulination test. At day 7 after primary immunization, the mean antibody titer against SRBCs was 9.14 +/- 3.02 in group A and 13.7 +/- 3.9 in group B (P < .05), while the mean antibody titer against E. coli was 14.8 +/- 8.5 in group A and 14.8 +/- 9.35 in group B. At day 16, the mean antibody titer against SRBCs was 13.71 +/- 3.9 in group A and 20 +/- 9.8 in group B, while the mean antibody titer against E. coli was 14.69 +/- 935 in group A and 26.67 +/- 8.26 in group B (P < .05). Four days after secondary immunization, the mean antibody titer against SRBCs was 13.33 +/- 4.62 in group A and 16 +/- 8.7 in group B, while the mean antibody titer against E. coli was 42.67 +/- 18.4 in group A and 69.33 +/- 31.4 in group B. It might be concluded that oral honey stimulates antibody production during primary and secondary immune responses against thymus-dependent and thymus-independent antigens.

Agglutination Tests↗
PubMed1984

True histiocytic lymphoma of the thymus. Report of a case and a study of the distribution of histiocytic cells in the fetal and adult thymus.

The thymus was the site of a true histiocytic lymphoma. Immunohistochemical demonstration of lysozyme and alpha-1-antitrypsin in the tumor cells indicated the histiocytic nature of the tumor. Five fetal and five adult thymus glands were studied for the presence and distribution of true histiocytic cells. Histiocytes were demonstrated predominantly in the connective tissue septa and constituted approximately 2% of cells in these thymuses. Histiocytes are therefore a normal constituent of the thymus, which may become the primary site of true histiocytic lymphoma.

Adult↗
PubMed1997

The thymus and self-tolerance: co-existence of encephalitogenic S100 beta-specific T cells and their nominal autoantigen in the normal adult rat thymus.

The adoptive transfer of auto-reactive T cells specific for S100 beta protein mediates experimental autoimmune panencephalomyelitis, an inflammatory autoimmune disease of the nervous system and eye. However, unlike classical encephalitogenic autoantigens which are components of the myelin membrane and restricted to the nervous system, S100 beta is expressed by many different cell types in a wide variety of peripheral tissues. We now report that S100 beta is also expressed within the rat thymus from embryonic day 16 through to adulthood at which time point the protein is localized within stroma cells of the thymic medulla. However, despite the continued expression of this autoantigen within the thymic microenvironment it proved possible to isolate encephalitogenic, S100 beta-specific CD4+ alpha beta TCR T cell lines from the naive adult rat thymus. These T cell lines were highly specific for S100 beta, and following activation in vitro and adoptive transfer initiate an inflammatory response in the central nervous system and eye of naive syngeneic recipients. These observations provide additional evidence that clonal deletion of autoaggressive T cell clones in the thymus is leaky. In this case allowing potentially autoaggressive T cell clones specific for S100 beta, a non-myelin autoantigen expressed in the nervous system, thymus and many peripheral tissues, to become an intrinsic component of the normal immune repertoire.

Animals↗
PubMed2006

Role of the thymus in transplantation tolerance in miniature swine: V. Deficiency of the graft-to-thymus pathway of tolerance induction in recipients of cardiac transplants.

BACKGROUND: We have previously shown that both thymic immigrants (graft to thymus pathway) and thymic emigrants (thymus to graft pathway) are involved in tolerance to renal allografts in miniature swine treated with a short course of calcineurin inhibitors. This study investigates the role of these pathways in cardiac transplant survival in recipients treated with a short course of tacrolimus. METHODS: Eleven animals received two-haplotype fully MHC-mismatched cardiac grafts with a 12-day course of tacrolimus. Recipients were thymectomized on day -21 (n=5) or day 0 (n=3), or were left euthymic (n=3). Two of the day -21 thymectomized animals received a day 0 host-MHC matched thymocyte infusion. RESULTS: Euthymic recipients of cardiac grafts treated with an immunosuppressive regimen identical to that previously shown to induce tolerance in euthymic recipients of renal allografts all rejected their grafts. Although no animal became tolerant, animals that were euthymic or thymectomized on day 0, as well as recipients of day 0 host-type thymocyte infusions following thymectomy on day -21, developed donor-specific hyporesponsiveness and maintained their cardiac grafts for markedly prolonged periods. In contrast, all animals thymectomized on day -21 that did not receive thymocyte infusions developed strong antidonor CTL responses and rejected their grafts by day 35. CONCLUSIONS: The graft-to-thymus pathway that plays an important role in tolerance induction to renal allografts appears to be relatively deficient in recipients of cardiac grafts. Strategies to increase donor antigen migration to the host thymus might therefore assist in tolerance induction to cardiac allografts.

Animals↗
PubMed1989

Acute thymus involution during infancy and childhood: immunohistology of the thymus and peripheral lymphoid tissues after acute illness.

We previously reported that the histologic grade of accidental involution of the thymus in infancy and childhood after a short period of acute illness correlates strongly with the duration of illness (Van Baarlen et al., Hum Pathol 1988;19:1155-60). We now extend this finding by reporting the phenotypic expression of thymus lymphoid and stromal cells. The thymic findings were correlated with changes in peripheral lymphoid organs. In the involuted thymus the immature and proliferating lymphoid populations that are present in the normal (uninvoluted) cortex were completely absent but the cortical epithelial network remained essentially intact even with increasing histologic grades of involution. Cells expressing the phenotype of subcapsular and medullary epithelium were found in this cortical stroma. In the subcapsular area, loss of expression of thymosin components alpha 1 and beta 4 was observed, without loss of epithelial cells. In the medulla a loss of cells expressing HLA-DR was observed, probably reflecting a loss of interdigitating cells. There was no correlation between changes in the thymus and peripheral lymphoid organs.

Acute Disease↗
PubMed1992

Pericapillary collagen in the human thymus: implications for the concept of the 'blood-thymus' barrier.

The deposition of collagen in the walls of capillary-size blood vessels was studied in 95 human thymuses with respect to the site of deposition, extent of the change and relation to age and degree of involution. When examined by electron microscopy the collagen was found to be situated between the 2 basement membranes of the so-called 'double-layered' capillaries characteristic of the thymus of many species. This results in the formation of substantial 'collars' of collagen around a proportion of the blood vessels examined. Few such collars are seen before birth, but their number and thickness increase markedly during the 1st year of life. The relationship of these changes to the degree of involution is less apparent. The significance of these changes to thymic structure and function is discussed in relation to cell traffic through the thymus and the postulated 'blood-thymus barrier', the existence of which is seen to be in some doubt.

Aging↗
PubMed1989

Differentiation of epithelial stroma during ontogenesis of the thymus in mice: a speculation on the origin of the thymus as a sensory organ.

Two monoclonal antibodies recognizing subpopulations of epithelial stroma cells of the embryonic mouse thymus are described. Antibody Th-115/7 reacts with epithelial cells of the thymus cortex: antibody Th-101/5 binds to stroma cells of the thymus medulla. In cryosections of whole embryos Th-115/7 bound in addition to mucosal epithelial cells of the pharynx, of the Th-101/5 stained submucosa cells of various regions of the pharynx, of the cavum nasi, of the tongue etc. These observations are compatible with the hypothesis that the thymus anlage originally had developed as a sensory organ at the entrance of the pharynx before it became a primary lymphoid organ.

Animals↗