Biomedical subjects

C Hiramine

Publications and source records attributed to C Hiramine.

At least 19 recordsLinked to original sources

PubMed2004

Phosphatidylserine receptor cooperates with high-density lipoprotein receptor in recognition of apoptotic cells by thymic nurse cells.

The thymus contains many apoptotic cells that arise from the process of positive and negative selection. Both thymic macrophages and thymic nurse cells/nursing thymic epithelial cells (nursing TECs), non-professional phagocytes, recognize and ingest apoptotic cells without inflammation or tissue damage. Previously we reported that human scavenger receptor class B (SR-B1) is involved in recognition of apoptotic thymocytes by nursing TECs. In this study, we examined the expression and role of a phosphatidylserine receptor (PSR). This receptor is believed to participate in the clearance of apoptotic cells. PSR was strongly expressed in nursing TECs. Transforming growth factor-beta augmented the expression of PSR leading to enhanced binding of apoptotic cells to nursing TECs. In nursing TECs, suppressed expression of human SR-B1 with anti-PSR antibody decreased binding of apoptotic thymocytes to nursing TECs. Our results suggest that both PSR and SR-B1 are expressed in nursing TECs and these receptors appear to play a major role in the clearance of apoptotic cells from the thymus.

Animals↗

PubMed2000

Human scavenger receptor B1 is involved in recognition of apoptotic thymocytes by thymic nurse cells.

Recognition and uptake of apoptotic cells by neighboring phagocytes is essential for the clearance of dying cells without accompanying inflammation or tissue damage. In the thymus, many apoptotic cells are generated in the process of negative selection, and both thymic macrophages (professional phagocytes) and nursing thymic epithelial cells (nursing TEC; nonprofessional phagocytes) recognize and ingest them. However the receptors responsible for this recognition and uptake have not been identified. In the present study, we have established a human nursing TEC line and examined the expression of several genes of the scavenger receptor family considered to be potential receptors for apoptotic cells. Human scavenger receptor-B1 (hSR-B1)/CLA-1, previously shown to recognize apoptotic cells, was strongly expressed in nursing TEC, whereas there was little or no expression of the other scavenger receptors tested: scavenger receptor class A, CD36, or CD68. Suppression of hSR-B1/CLA-1 expression using antisense oligonucleotides decreased the binding of apoptotic thymocytes to nursing TEC by more than 40%. These results indicate that hSR-B1/CLA-1 may play a major role in the clearance of apoptotic cells in the thymus, mediating the recognition and ingestion of apoptotic thymocytes by nursing TEC.

Animals↗

PubMed2000

Interaction of merosin (laminin 2) with very late activation antigen-6 is necessary for the survival of CD4+ CD8+ immature thymocytes.

The laminin alpha2-chain is a component of merosin, a member of the laminin family molecules, which is mainly expressed in the basement membranes of striated muscle. It is known that laminin alpha2 gene (lama2) null mutant mice (dy3k/dy3k) exhibit congenital muscular dystrophy (CMD). Because the laminin alpha2-chain is also expressed in the thymus, the role of merosin in the thymus was examined. In association with the onset of muscular dystrophy, CD4+ CD8+ double-positive (DP) thymocytes disappear by apoptotic cell death, while CD4+ CD8- or CD4- CD8+ thymocytes remain. In order to study the mechanisms leading to the selective death of DP cells in the absence of merosin, the role of the interaction between very late activation antigen-6 (VLA-6), a candidate merosin ligand in the thymus, and merosin was examined. The in vitro survival of thymocytes from normal mice was maintained by the addition of either anti-VLA-6 monoclonal antibodies (mAbs) or merosin. Furthermore, when the normal thymocytes were cultured on thymic epithelial cell lines, viable DP cell recoveries on wild-type epithelial cells were better than on cells from null mutant mice. The results suggest that DP cells are more sensitive to an uncharacterized apoptotic death signal, and that survival is supported by the interaction between VLA-6 and merosin.

Animals↗

PubMed1999

Decrease in apoptosis of germ cells in the testes of infertile men with varicocele.

To determine whether the regulation of apoptosis in the testes of patients with varicocele testes was abnormal, affecting germ-cell differentiation and sperm production, we studied apoptosis in the testes of normal men and infertile men with varicocele. In all, 56 testicular biopsy specimens were collected from 28 varicocele patients. The specimens from the testes of five normal volunteers with informed consent were used as controls. In situ end-labeled cells were counted with a CAS 200 image analyzer, and an apoptotic index (AI) was calculated by division of the number of labeled cells by the total number of spermatocytes and spermatogonia in over 20 seminiferous tubules. The apoptosis was also examined by electron microscope. The mean AI was 9.67 +/- 0.93% in normal testes (n = 5). In contrast, the mean AIs determined in the right and left testes of varicocele patients (n = 28) were 3.90 +/- 2.28% and 3.78 +/- 2.87%, respectively. The AIs recorded for the testes of varicocele patients were significantly lower than those noted for normal men (P < 0.05). In varicocele patients the AI obtained in the right testis was not statistically significantly different from that found in the left testis. The numbers of apoptotic cells per Sertoli cell also decreased in the testes of varicocele patients as compared with normal men (P < 0.01). Evaluation of all specimens, including the normal controls, revealed no significant correlation either between the AI and the sperm concentration on the seminogram or between the AI and Johnsen's mean score. There was also no relationship between the AI and the serum level of follicle-stimulating hormone, lutenizing hormone, testosterone, or estradiol. In conclusion, apoptosis is decreased in germ cells in the testes of infertile men with varicocele as compared with normal men.

Adult↗

PubMed1997

[Definition and morphological features of apoptosis].

The term apoptosis, an ancient Greek word used to describe the "falling off" of petals from flowers or leaves from trees, was proposed by Kerr, Wyllie and Currie in 1972 to refer to the peculiar morphology of physiologically occurring cell death which plays a complementary but opposite role to mitosis in the regulation of animal cell populations. Apoptosis is opposed to necrosis-the appearance of accidental and pathological cell death. Apoptosis involves loss of microvilli, smooth-surfaced protuberances, chromatin condensation, nuclear and cytoplasmic condensation, loss of cell volume, and nuclear fragmentation. At an early stage, condensed chromatin tends to marginate in crescents around the nuclear envelope in most cell types, but in certain cells such as thymocytes, it often occupies much of the nuclear volume. Contrasted to necrosis, in apoptotic cells there are neither swelling and rupture of cytoplasmic organelles and plasma membranes nor inflammatory reaction. Apoptotic cells break up into membrane bound apoptotic bodies and they are phagocytosed by nearly resident tissue cells. These morphological changes are often accompanied by the internucleosomal DNA fragmentation. Apoptosis is a representative morphology of programmed cell death (PCD) which occurs within a developmental context in response to a definable physiological stimulus and requires de novo gene expression. However, apoptosis should not be considered synonymous with PCD. Because, there are examples of non-apoptotic PCD and pathological stimuli such as mild cell injury can induce apoptosis.

Animals↗

PubMed1996

Thymic nurse cells as the site of thymocyte apoptosis and apoptotic cell clearance in the thymus of cyclophosphamide-treated mice.

Structural changes in the thymus of BALB/c mice after the intraperitoneal injection with a single high dose (200 mg/kg) of cyclophosphamide (CY) were examined. A large number of thymic nurse cell (TNC)-like structures that contained apoptotic thymocytes were observed in the thymus between 8 and 20 hours after CY treatment, just before a marked reduction in the number and proportion of PNAhi, CD3-, CD4+ CD8+ thymocytes. The majority of apoptotic thymocyte-containing TNC-like structures had an epithelial nature and were mainly located in the subcapsular and outer cortex, perivascular area of the cortex, corticomedullary junction and, in part, in the medulla. Most thymocytes seemed to undergo apoptosis synchronously in every TNC-like structure, but one or two fully intact mature thymocytes were found in every one. By 24 hours after CY treatment, many vacuoles that contained apoptotic cells in various stages of degeneration were observed within the epithelium, and most of the apoptotic cells disappeared at 24 hours. We herein demonstrated that the epithelium of TNC-like structures had a phagocytic activity in the digestion of apoptotic thymocytes by the presence of phagolysosomes with acid phosphatase activity. The epithelium left very small vacuoles with a small amount of nondigestible dense granules. The minority of apoptotic thymocyte-containing TNC-like structures scattered in the entire cortex between 8 and 20 hours after CY treatment was macrophage (M phi)-derived. Many apoptotic cell-containing M phi were observed as early as 4 hours after the CY injection. Apoptotic thymocytes of CY-treated mice showed the internucleosomal DNA fragmentation. In conclusion, CY accelerates physiologic thymocyte apoptosis, and epithelial TNC are one of the principal sites of thymocyte apoptosis as well as an environment for the nursing of immature thymocytes. Both the epithelium of TNC and M phi participate in digestion of apoptotic cells and have the efficient capacity of clearance of apoptotic thymocytes in the normal thymus at a presumed high rate.

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PubMed1995

Murine nursing thymic epithelial cell lines capable of inducing thymocyte apoptosis express the self-superantigen Mls-1a.

Two cloned thymic epithelial cell (TEC) lines, D2.TEC-A3 and AKR TEC-K1, were established from minor lymphocyte-stimulating (Mls)-1a-positive normal, 4-week-old DBA/2 (H-2d, Mls-1a2a) mice and AKR (H-2k, Mls-1a2b) mice, respectively. Both cell lines were MHC class I and class II (both I-A and I-E) positive without stimulation by interferon-gamma. They were capable of infolding immature thymocytes to form thymic nurse cells (TNC; we call this type of TEC "nursing TEC") and induced apoptosis with DNA fragmentation in immature thymocytes. Using a primary Mls mixed lymphocyte reaction (MLR) we demonstrated that self-superantigen Mls-1a was expressed on these cloned nursing TEC lines. D2.TEC-A3 cells stimulated nylon-wool-purified splenic T cells obtained from H-2d-compatible BALB/c (Mls-1b2a) and B10.D2 (Mls-1b2b) mice with a maximal response at a stimulator:responder ratio of 1:40 after 4 days of the coculture. AKR TEC-K1 cells also stimulated purified T cells from H-2k-compatible C3H/He mice (Mls-1b2a) in a similar manner. The Mls MLR induced by the nursing TEC lines was completely inhibited in the presence of anti-mouse I-A and anti-mouse I-E monoclonal antibodies. These results suggest that nursing TEC/TNC could be involved in negative selection due to apoptosis.

Animals↗

PubMed1994

Generation and characterization of a continuous line of CD8+ suppressively regulatory T lymphocytes which down-regulates experimental autoimmune orchitis (EAO) in mice.

We have previously shown that two injections with viable syngeneic testicular germ cells (TC) alone developed experimental autoimmune orchitis (EAO) in C3H/He mice, and that the induction of antigen-specific tolerance in this EAO model is associated with the generation of antigen-specific suppressively regulatory T (Ts) cells. For the elucidation of the nature of these Ts cells, a murine Ts cell line (designated Ts-A) was established. This line was generated from the spleen cells of C3H/He mice which had received three i.v. injections of a soluble (deaggregated) form of murine testicular antigen (mTA), followed by the repeated selection of these spleen lymphocytes in vitro by stimulation with mTA. Adoptive transfer of Ts-A cells into naive syngeneic mice immediately before the first TC injection was found to downgrade EAO in actively immunized recipients. The transferred Ts-A cells significantly inhibited the cellular immune response to TC in the recipients in an antigen-specific manner, but these cells had no inhibitory effect on the humoral immune response to TC. This line could also inhibit in vitro syngeneic TC-driven proliferation of orchitogenic lymphocytes. Surface phenotype of this line was CD8+, CD4-, Thy-1.2+, CD3+, and TCR alpha beta+. These findings may suggest an in vivo role for suppressively regulatory lymphocytes, capable of inhibiting helper T cells, in the regulation of EAO.

Animals↗

PubMed1994

[Chronological changes in autoantigenicity of autologous testicular germ cells in C3H/He mice during the postnatal period].

Our recent studies demonstrated that experimental autoimmune orchitis (EAO) model was produced in C3H/He mice with high incidence by two subcutaneous injections of viable syngeneic testicular germ cells (TC) without the use of any adjuvants or immunopotentiators. In this study the developmental patterns of autoantigenicity of TC during postnatal period were investigated by examining the orchitogenic activity of TC, the lymphostimulatory activities of TC (including the TC-induced in vitro lymphocyte proliferative response and the cytokine release from sensitized spleen cells (SPC) in response to TC) and the immunohistochemical localization of target autoantigens in the testes of mice at various weeks of age. Delayed-type hypersensitivity-inducing capacity and anti-TC antibody-eliciting capacity were initially observed in mice that were immunized with TC of 4-week old (w.o.) mice. The TC from 6-w.o. mice had the capability of inducing EAO (orchitogenicity) for the first time. A significant stimulation of in vitro lymphocyte proliferative response, as well as of interleukin (IL) 5 and IL-6 production by sensitized SPC were detectable when TC of mice 3-w.o. or more than were employed as stimulant. IL-2 and interferon gamma production were detected with TC of 4-w.o. mice. Immunohistochemical staining reaction with anti-TC antisera was primarily localized at the acrosomal portion of spermatids and spermatozoa in the seminiferous tubules, being already detected in spermatids of as early as 3-w.o. mice. Thus, from these data it is suggested that the appearance of the lymphostimulatory activities of TC consistently precedes that of the orchitogenic activity and that relatively mature germ cells such as spermatids and spermatozoa developing in the testes during the postnatal weeks may be responsible for the induction of disease and relevant immune responses in our EAO system.

Animals↗

PubMed1993

A 60-kDa thymic epithelial cell surface protein as a potent molecule mediating the cellular interaction with immature T cells.

A unique 60-kDa surface protein expressed on the thymic epithelial cells was characterized as a potent molecule participating in the interaction between thymic stromal cells (TSC) and immature T cells. Previously, we reported an athymic mouse-derived T cell clone, N-9F, which proliferates on TSC. In the present study, we established a TSC clone, SL10.3, from a BALB/c mouse. SL10.3 has an epithelial cell nature and supports N-9F and fetal thymocytes growth in vitro. The two rat monoclonal antibodies, AS19 and AS32, directed to the SL10.3 cell surface inhibited N-9F and fetal thymocytes growth on SL10.3, suggesting that the reactive molecule may mediate the cellular interaction between TSC and immature T cells. Both antibodies are directed to the same 60-kDa protein with a pI point of 5.4, but to different epitopes on the protein. The 60-kDa protein is distributed on thymic epithelial cells, fibroblasts, and vascular endothelial cells, but not on the hematopoietic cells tested.

Animals↗

PubMed1993

Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. I. Comparison of pathology, delayed type hypersensitivity, and antibody.

In the present study, it was demonstrated that there were marked strain differences in susceptibility to the induction of our new murine model of experimental autoimmune orchitis (EAO; definite orchitis with hypospermatogenesis) induced by two or three sc injections with viable syngeneic testicular germ cells (TC) without any adjuvants. Among 12 inbred strains of mice examined, the A/J (H-2a), C3H/He (H-2k), and C3H/HeN (H-2k) strains were highly susceptible, whereas the C57BL/6N (H-2b), C57BL/10Sn (H-2b), BALB/cAnN (H-2d), AKR/N (H-2k), CBA/JN (H-2k), C3H/HeJ (H-2k), and MRL/lpr (H-2k) strains were low susceptible, and the DBA/2N (H-2d) as well as C3H/BiKi (H-2k) strains were resistant. In particular, mice of the H-2k haplotype demonstrated varying degrees of susceptibility, from highly to totally resistant, to the induction of EAO. Disease susceptibility to this type of EAO does not seem to be associated with a particular H-2 haplotype. All mice of the highly susceptible strains that received two injections of TC (TC x 2) developed a significant increase in both levels of delayed footpad reaction (DFR) to TC and anti-TC antibodies measured by ELISA. In the low susceptible and the resistant strains receiving TC x 2 or TC x 3, there was no correlation between the immune responses and the susceptibility to disease in these strains, with the exception of the BALB/cAnN mice receiving TC x 3. The low susceptible and the resistant mice that received TC x 2 were classified into four groups based on the DFR and antibody response: the C57BL/6N, BALB/cAnN, CBA/JN, and C3H/HeJ strains were both positive, and the C57BL/10Sn and AKR/N strains were both negative or very low; the DBA/2N and MRL/lpr strains showed negative DFR and positive antibody response, and the C3H/BiKi strain showed quite the opposite. Almost all mice of the 12 inbred strains that received TC x 3 showed positive antibody response, although its level varied. There seems to be no linkage between the cell-mediated and humoral immune responses and the H-2 locus in our new EAO model.

Animals↗

PubMed1993

Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. II. Analysis on susceptibility to EAO induction using F1 hybrid mice and adoptive transfer system.

In our novel murine model of experimental autoimmune orchitis (EAO) induced by two or three injections of viable syngeneic testicular germ cells (TC) alone, significant differences in susceptibility to the induction of EAO were found, and the disease susceptibility did not seem to be associated with a particular H-2 haplotype. The H-2 identical background disparate (highly susceptible x low susceptible)F1 hybrids, (C3H/He x C3H/HeJ)F1 and (C3H/HeJ x C3H/He)F1 mice, were highly susceptible to the induction of EAO. The H-2 identical background disparate (highly susceptible x resistant)F1 hybrids, (C3H/He x C3H/BiKi)F1 and (C3H/BiKi x C3H/He)F1 mice, were low susceptible to the induction of EAO. Both the H-2 and background disparate (highly susceptible x resistant)F1 hybrids, (C3H/He x DBA/2N)F1 and (DBA/2N x C3H/He)F1 mice, were equally resistant to EAO induction. In the susceptible hybrids, both delayed footpad reaction (DFR) and antibody responses to TC increased. On the other hand, in the resistant hybrids, the levels of anti-TC antibodies were elevated but the DFR to TC remains depressed. This suggests that the antibody production and induction of DFR may be under different genetic controls and that cellular immunity plays an important role in this EAO induction. In order to search for the mechanistic basis for low susceptible C3H/HeJ and resistant C3H/BiKi mice, these mice received orchitis-inducible spleen cells (SPCs) from C3H/He mice. C3H/HeJ mice were highly susceptible to passive EAO. In contrast, disease-resistant C3H/BiKi mice failed to develop passive EAO. In addition, we examined whether or not regulatory cells capable of preventing the disease induction were generated in low susceptible C3H/HeJ and resistant C3H/BiKi mice immunized with TC. Transfer of SPCs from TC-immunized C3H/HeJ and C3H/BiKi mice into C3H/He mice before the EAO challenge had no suppressive effect on subsequent disease induction.

Animals↗

PubMed1993

Murine experimental autoimmune orchitis (EAO) induced by syngeneic testicular germ cells (TC) alone: orchitogenic and lymphostimulatory activities of TC from mice at various ages.

As part of our continuous investigations on the immune pathogenesis of a new experimental autoimmune orchitis (EAO) model without the use of adjuvant in C3H/He mice, the developmental patterns of autoantigenicity of viable syngeneic testicular germ cells (TC) during the postnatal period were investigated by examining the orchitogenic and immunogenic activities of TC, the lymphostimulatory activities of TC (the cytokine release from sensitized spleen cells (SPC) in response to TC), and the immunohistochemical localization of autoantigens in the testes of normal mice at various weeks of age. TC from 6-week-old mice had the capability of inducing EAO (orchitogenicity) for the first time. Delayed-type hypersensitivity-inducing capacity and anti-TC antibody-eliciting capacity were initially observed in mice immunized with TC from 4-week-old mice. A significant stimulation of interleukin 5 (IL-5) and interleukin 6 (IL-6) production by sensitized SPC was detectable when the TC from 3-week or older mice were employed as a stimulant. Interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) production was detected with TC from 4-week or older mice. Immunohistochemical staining reaction with anti-TC antisera was primarily localized at the acrosomal portion of spermatids and spermatozoa in the seminiferous tubules and was detected in early and late spermatids of mice as early as 3 weeks. Thus, from these chronological data it is suggested that the appearance of the lymphostimulatory activities of TC consistently precedes that of the orchitogenic activity and that the production of IL-5 and IL-6 (Th 2 cytokine) by sensitized SPC upon in vitro TC stimulation is detectable earlier than the production of IL-2 and IFN-gamma (Th 1 cytokine) in the postnatal period.

Aging↗

PubMed1992

Inhibition of a novel model of murine experimental autoimmune orchitis by intravenous administration with a soluble testicular antigen: participation of CD8+ regulatory T cells.

Recently, we established a novel murine model of experimental autoimmune orchitis (EAO) in C3H/He mice by means of two sc injections of 1 x 10(7) viable syngeneic testicular germ cells (TC) without the use of any adjuvants. Using this model, an effective and reproducible system of immunoregulation in EAO was developed. The induction of this EAO was suppressed by pretreatment with five iv injections of a soluble (deaggregated) form of murine testicular antigen (mTA). The antigen, mTA, was prepared by acid extraction and ammonium sulfate precipitation of defatted testes and epididymides. The development of EAO and relevant delayed-type hypersensitivity was suppressed in an antigen-specific fashion, but anti-TC antibody formation was not affected. A single dose of cyclophosphamide at 2 days after the tolerogenic regime abrogated the unresponsiveness to EAO. Three doses of recombinant interleukin 2 at every other day starting on the next day of the last pretreatment did not overcome the unresponsiveness to EAO. CD8+ T cells isolated from the spleen of deaggregated mTA-pretreated animals could adoptively transfer suppression against EAO into naive recipients, whereas CD4+ T cells failed to transfer the suppression.

Animals↗

PubMed1992

Suppression of efferent limb of testicular autoimmune response by a regulatory CD4+ T cell line in mice.

A murine T cell line (designated as C.Ts) as a mediator of suppression of experimental autoimmune orchitis (EAO) was established. The method of establishment of C.Ts cell line was preparing spleen cells from C3H/He mice hyperimmunized with testicular germ cells (TC) and the repeated selection of the lymphocytes in vitro by stimulation with mouse testicular antigens (mTA). The C.Ts cells were Thy1.2+, surface immunoglobulin-, CD3+, CD4+ and CD8-. The cells could suppress the induction of EAO when transferred into actively EAO-sensitized mice only at the pre-clinical stage of the disease (efferent limb of the autoimmune response). The transferred C.Ts cells significantly inhibited both cellular and humoral immune responses to TC in the recipients in an antigen-specific manner. The disease suppression by C.Ts cells was found to depend upon their cell number, and their suppressive activity was markedly augmented by in vitro stimulation with mTA.

Animals↗

PubMed1992

Establishment of an experimental model of autoimmune epididymo-orchitis induced by the transfer of a T-cell line in mice.

A murine T-cell line derived from BALB/c mice (designated B.T.1) was established which was capable of adoptively transferring experimental autoimmune orchitis (EAO) in normal recipients. The protocol consisted of preparing lymphocytes obtained from the mice that were immunized with syngenetic testicular germ cells (TGC) and the subsequent repeated selection of the lymphocytes in vitro by stimulation with murine testicular antigens (mTA). Phenotypic analysis revealed that B.T.1 cells were CD4+ T-cells. Intra-peritoneal inoculation of as few as 1 x 10(5) B.T.1 cells, that were stimulated in vitro with mTA before the inoculation, was capable of transferring EAO to naive recipients. In the latter, both delayed type hypersensitivity (DTH) and humoral responses to TGC were augmented. The transferred lesion was characterized by infiltration of inflammatory cells into the epididymis and rete testis and widespread aspermatogenesis in the testis. The transfer of EAO was unsuccessful when the recipients received B.T.1 cells that were maintained in culture medium without stimulation with mTA. In these recipients, anti-TC DTH was not detected, although the specific humoral response was observed. In-vitro characterization of the biological activity of B.T.1 cells revealed that the line had no cytolytic activity against TGC but the culture supernatant had macrophage migration inhibitory activity involved in the DTH response. Therefore, the DTH responsiveness transferred by B.T.1 cells was found to correlate with their orchitis-inducing capacity.

Animals↗

PubMed1991

A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. I. Immunological and histological studies.

Experimental autoimmune orchitis (EAO) was produced in C3H/He mice with as high as 100% incidence by two or three s.c. injections of 1 x 10(7) viable syngeneic testicular germ cells (TC) without resorting to adjuvants, Bordetella pertussis vaccine, or other immunological manipulations. On day 40 after the first injection of TC, the lesions induced were characterized by interstitial infiltration of inflammatory cells and severe hypospermatogenesis in the testis with resulting whole organ atrophy and, in contrast, by a complete lack of epididymitis. Immunological studies revealed that this form of immunization caused both delayed-type hypersensitivity and humoral antibody responses to syngeneic TC. We compared the susceptibilities to the induction of this type of EAO among six different strains of inbred mice comprising A/J, AKR, BALB/c, C3H/He, C57BL/6 and DBA/2 mice. All strains except for DBA/2 mice developed lesions of EAO to a greater or lesser extent, and severe disease was induced with high frequency in two strains, C3H/He and A/J. As this murine model of EAO can be induced without the use of Freund's complete adjuvant and B. pertussis vaccine, it is simply 'autoimmune' in nature and may provide new ways for further investigation into the immunological mechanisms which regulate deleterious autoimmune reactions to germ cell antigens leading to the male infertility.

Animals↗

PubMed1991

A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. II. Immunohistochemical findings of fully-developed inflammatory lesion.

Previous studies demonstrated that experimental autoimmune orchitis (EAO) was produced in C3H/He mice with very high incidence by two or three subcutaneous injections of viable syngeneic testicular germ cells, without the use of any adjuvants or immunopotentiators and that the disease induced was characterized by a complete lack of epididymitis despite a definite orchitis with hypospermatogenesis. In this report, immunohistochemical characterization of immune cells in the fully-developed orchitic lesion was carried out using monoclonal antibodies and immunoperoxidase staining. Thy-1.2+ cells, Mac-1+ cells, B220+ cells and cytoplasmic Ig-bearing cells in the lesion were estimated to be approximately 30, 15, 20 and 30% of all inflammatory cells, respectively. Major phenotype of T cells in the lesion was CD4+ (approximately 85%) with the remainder (approximately 15%) being CD8+. The percentages of cytoplasmic IgG-, IgA- and IgM-bearing cells were estimated as approximately 35, 60 and 5% of all cytoplasmic Ig-bearing cells, respectively. Deposits of immunoglobulins and third component of complement were identified on the basement membrane of the seminiferous tubules, interstitium between the tubules, vessel endothelium and degenerated germ cells in the lesion. Circulating antibodies directed against the acrosomal portion of germ cells were detected in IgG and IgM classes but not in IgA class. Inflammatory cells (including macrophages, B cells and, probably, activated T cells) in the lesion were Ia+, but Leydig cells, Sertoli cells and germ cells did not stain for Ia at all.

Animals↗