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Adoptive transfer of suppression of experimental allergic orchitis with lymphoid cells from antigen-pretreated guinea pigs.

The injection of lymph node cells or spleen cells, obtained from strain 13 guinea pigs rendered unresponsive to experimental allergic orchitis (EAO) by pretreatment with testicular antigen (TA) in incomplete Freund's adjuvant, into normal syngeneic recipients markedly prevented the development of EAO, especially of the interstitial inflammatory cell response, which was expected to occur 2 weeks following orchitogenic challenge with TA in complete Freund's adjuvant (CFA). The suppressive effect of thymus cells from the same donors was much less prominent. The inhibition of EAO by suppressor cells was specific for the relevant antigen TA. In such EAO-suppressed animals delayed skin reaction to TA was suppressed, whereas antisperm antibody formation was not impaired. The active suppressor cells residing in the lymph nodes had characteristics of T lymphocytes, in that they did not adhere to the plastic dish surface and nylon wool and in that they formed rosettes with rabbit erythrocytes. B lymphocytes from the same animals did not have detectable suppressive properties. Lymph node cells from protected donors that had been treated with a single dose of cyclophosphamide (CY) 3 days before cell transfer were unable to transfer unresponsiveness to EAO. The results suggest that the immune prevention against EAO is explainable at least in part by the generation of CY-sensitive suppressor T lymphocytes with the capacity of inhibiting development of effector T cells after antigenic stimulation and that suppressor cells that mediated unresponsiveness to EAO may also regulate the cellular hypersensitivity to TA.

Animals↗

An analysis of the role of tumor necrosis factor in the phenotypic expression of actively induced experimental allergic orchitis and experimental allergic encephalomyelitis.

The role of tumor necrosis factor (TNF) was examined in the pathogenesis of actively induced experimental allergic orchitis (EAO) and experimental allergic encephalomyelitis (EAE) in the mouse. The ability of TNF to function as either an adjuvant or to replace pertussigen in eliciting active EAO was examined by treating groups of mice immunized for disease induction with 10 micrograms of recombinant murine TNF at various time points throughout both the induction and effector phases of the disease process. All groups of animals receiving TNF ranging from 2 days before antigen challenge to 26 days postimmunization failed to exhibit significant disease in comparison to animals treated with pertussigen, indicating that TNF can neither serve as an adjuvant nor replace pertussigen in eliciting active disease. Similarly, the role of TNF in the pathogenesis of EAO and EAE was investigated by examining the ability of a known neutralizing rabbit anti-TNF IgG antibody preparation to either inhibit the development or decrease the severity of the clinical symptoms and/or the inflammatory lesions associated with the disease processes. Groups of either B6AF1 hybrid or SJL/J mice were immunized for the induction of active EAO and EAE, respectively. They were passively immunized with either 2 mg of purified anti-TNF IgG or control anti-CFA IgG at time points ranging from 2 days before to 28 days after antigen challenge. All groups, regardless of the day of treatment with anti-TNF IgG, did not exhibit a markedly significant difference in disease outcome in comparison to either groups receiving no antibody or passively immunized with anti-CFA IgG. Taken together, these results suggest that TNF does not appear to be the principal cytokine/lymphokine involved in the pathogenesis of actively induced EAO and EAE.

Animals↗

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↗

Transfer of susceptibility to experimental autoimmune orchitis from responder to non-responder substrains of BALB/c mice.

Substrains of BALB/c mice differ in their susceptibility to experimental autoimmune orchitis (EAO), with BALB/cJ representative of the non-responders and BALB/cBy representative of the responders. We examined whether the susceptibility of these two substrains could be altered by reciprocal adoptive transfer of lymphoid cells. The cells transferred were of three types, normal spleen cells, T cell-enriched spleen and lymph node cells from mice immunized with testis homogenate (TH) in complete Freund's adjuvant (CFA) and given an extract of Bordetella pertussis (BP) and the latter cells activated by in vitro culture with TH antigen for 48 h. Controls were given buffer alone. Cell or buffer recipients were immunized with TH + CFA + BP three weeks later and examined for testicular histopathology 25-28 days after immunization. The cultured, immune T-enriched cells were consistently effective in transferring susceptibility from BALB/cBy to BALB/cJ. In the reverse experiments, non-responsiveness could be transferred from BALB/cJs to BALB/cBys most effectively with immune, non-cultured T-enriched cells. Transfer of cultured, immune T-enriched cells from BALB/cJs to other BALB/cJs had no significant effect on susceptibility to EAO. The results suggest that susceptibility to EAO in BALB/c mice depends on the T cell responses in the mice and not on differences at the level of the testis.

Animals↗

Experimental allergic orchitis in mice. VII. Preliminary characterization of the aspermatogenic autoantigens responsible for eliciting actively and passively induced disease.

Experimental allergic orchitis (EAO) can be induced actively and passively in mice by either immunization with mouse testicular homogenate (MTH) in conjunction with the appropriate adjuvants or by transferring CD4+ T cells isolated from sensitized donors into non-immunized, naive recipients. The distribution of inflammatory lesions seen in active and passive EAO are markedly different. In active EAO maximal disease is observed in the seminiferous tubules, whereas in passive EAO lesions occur primarily in the straight tubules, rete testis, and ductus efferentes. These observations suggest that different immunopathogenic mechanisms and/or aspermatogenic autoantigens may be responsible for the distinct histopathologic profiles. Two murine testis-specific aspermatogenic autoantigens (mAP1 and mAP2) were partially purified from MT acetone powder by extraction in 7-M urea under reducing conditions, gel filtration, ion-exchange chromatography, and preparative isoelectric focusing from pH 3 to 10. In gel filtration on Sephacryl S-400 in 7-M urea, mAP1 is confined to the V0 peak, while mAP2 is in the major included peak. mAP1 has an isoelectric point of 4.4-4.9, is sensitive to both pronase and DNase but not RNase, and is active at a minimal dose of 250-500 micrograms (dry wt). Dose-response bioassays for active and passive EAO revealed that mAP1 preferentially elicits active disease, whereas mAP2 is most effective at eliciting passive disease. These results support the concept that the different histopathologic profiles seen in active and passive EAO are, in part, the result of different immunopathologic responses elicited by separate aspermatogenic autoantigens.

Animals↗

Characterization of (-)-(3H)-DHA binding to intact mouse lymphocytes: effect of experimental autoimmune orchitis on beta-adrenoceptor expression.

Autoimmune orchitis induced an increment in the beta-adrenoceptor populations in intact mouse lymphocytes, depending on their source. Characterization of (-)-(3H)-DHA specific binding to intact normal cells indicate that thymic cells do not have the ability of binding a beta-adrenergic ligand. In contrast, spleen and lymph node cells showed a homogeneous population of beta-adrenergic receptors. (-)-(3H)-DHA binding was a rapid, reversible and stereospecific process. Competition experiments indicated the order of potency of the agonists and led to their definition as being of the beta 2-adrenoceptor subtype. Saturation assays and Scatchard analysis indicated a single class of binding sites (being free of allosteric or cooperative interaction) in both control and immune cells. However, spleen and lymph node cells from mice hyperimmunized with testicular preparations showed a marked increase in the number of beta-adrenoceptor sites with no changes in chi d. These results emphasize the use of lymphocytes possessing a homogeneous population of beta 2-adrenoceptors as an easily available model for monitoring beta-adrenoceptors in disease.

Alprenolol↗

West Nile virus encephalitis with myositis and orchitis.

This report documents the hospital course and autopsy findings of a 43-year-old man with a renal allograft who died of West Nile virus (WNV) encephalitis. Central nervous system (CNS) findings were those of severe necrotizing and hemorrhagic encephalitis affecting gray matter regions limited to the diencepahlon, rhombencephalon, spinal cord, and limbic system. The bilateral process exhibited preferential involvement of motor neurons. Brain imaging obtained 6 days before death demonstrated an unusual pattern of involvement corresponding with the autopsy findings, confirming that imaging may be a specific diagnostic guide in WNV encephalitis. Extra-CNS findings include myositis with T-lymphocyte infiltration of nerve fibers, suggesting that the virus may reach the CNS via peripheral nerves. Orchitis with dense T-lymphocyte infiltration and syncytial cell formation thought to be due to WNV were also noted.

Adult↗

Orchitis as an unusual manifestation of human African trypanosomiasis.

African trypanosomiasis is a re-emerging disease. We report the case of an African patient whose predominant symptom was infertility due to a granulomatous orchitis. The patient was afebrile and had not been in Africa for years. Lymphadenopathy and splenomegaly led us eventually to the diagnosis of sleeping sickness. After treatment with suramin his spermiogram returned to normal. Sleeping sickness evolves through clinically different stages and leads to death if left untreated. The disease may, however, present clinically extremely variable and may thus be difficult to diagnose.

Adult↗

Xanthogranulomatous orchitis.

Xanthogranulomatous inflammation is an uncommon process that is usually associated with severe renal infection. We report a case of a 64-year-old man with xanthogranulomatous inflammation in the testis who presented with contralateral epididymoorchitis and a painless testicular mass. Only two prior cases of xanthogranulomatous orchitis have been reported. This case highlights the need for a broad differential diagnosis when approaching testicular masses, particularly in the setting of coincident infection.

Diagnosis, Differential↗

Late occurrence of bilateral tuberculous-like epididymo-orchitis after intravesical bacille Calmette-Guérin therapy for superficial bladder carcinoma.

We report a case of bilateral tuberculous-like epididymo-orchitis occurring 3 years after intravesical bacille Calmette-Guérin instillation therapy in an 83-year-old patient with proven superficial bladder carcinoma. The patient had no previous history of tuberculosis. Because of persistent inflammation and painful swelling of the epididymides and testes, the patient underwent bilateral orchiectomy. This case demonstrates the late adverse effects that can occur after intravesical BCG therapy, which in our patient ended in surgical removal of both gonads.

Adenocarcinoma↗

Epididymo-orchitis and testicular abscess due to Nocardia asteroides complex.

Nocardia asteroides complex is a rare human pathogen chiefly affecting immunosuppressed patients. We present the sixth case of epididymo-orchitis attributable to this organism. A 78-year-old man presented to the Mayo Clinic with fever and weight loss after being treated with cyclophosphamide and prednisone for an immune-mediated vasculitis. He was found to have a testicular abscess, and orchiectomy was performed. N. asteroides complex was identified on the wound cultures. Sulfa therapy was begun. In previous case reports, this condition carried a 50% mortality rate. Patients who survive seemed to benefit from aggressive surgical debridement and long-term sulfa therapy.

Abscess↗

Tuberculous epididymitis and epididymo-orchitis: sonographic findings.

The findings at scrotal sonography in 10 patients with tuberculous epididymitis and in 2 with nontuberculous epididymitis are presented. In 6 patients with tuberculous epididymitis the testes were also involved (epididymo-orchitis). The most notable sonographic findings of tuberculous epididymitis were an enlarged epididymis, predominantly in the tail portion, and marked heterogeneity of the echo texture of the involved epididymis. Sonographic findings of associated testicular involvement consisted of a diffusely enlarged hypoechoic testis or ill defined focal intratesticular hypoechoic areas, or an irregular margin between the testis and epididymis. The sonographic findings encountered in patients with tuberculous epididymitis appear to be different from those encountered in nontuberculous epididymitis. Sonography might prove helpful in aiding the clinical distinction between these 2 forms of epididymitis and in demonstrating associated testicular involvement in tuberculous epididymitis.

Adult↗

Epididymo-orchitis developing as a late manifestation of intravesical bacillus Calmette-Guerin therapy and masquerading as a primary testicular malignancy: a report of 2 cases.

In 2 cases epididymo-orchitis, indistinguishable from a testicular tumor, developed as a late (15 and 34 months, respectively) complication following use of Tice strain bacillus Calmette-Guerin for treatment of superficial bladder carcinoma. In each instance the lesion was asymptomatic and ultrasonography demonstrated a complex scrotal mass. Inguinal orchiectomy was performed for diagnosis and therapy. The importance of obtaining a mycobacterial culture for further therapy planning is stressed.

Administration, Intravesical↗

Schistosomal orchitis simulating malignancy.

We report a case of schistosomal orchitis simulating malignancy. The patient presented with a unilateral hydrocele, testicular enlargement and loss of testicular sensation. Orchiectomy was performed because of suspected malignancy. Tissue diagnosis was schistosomiasis. The incidence, pathogenesis and pathology of genital schistosomiasis are discussed, and the literature is reviewed.

Diagnosis, Differential↗

Type B Hemophilus influenzae epididymo-orchitis in the prepubertal boy.

The ninth pediatric case of type B Hemophilus influenzae epididymo-orchitis is reported and the literature is reviewed. This is a manifestation of systemic infection and these children often are toxic at presentation. Scrotal fluid cultures may be sterile if inappropriate culture media are used. The urinary tract is not the primary source of infection and radiographic correlation has not proved to be valuable. Antibiotic therapy may need to be prolonged in selected cases. Testicular atrophy has not been noted in these children at followup.

Child, Preschool↗

Epididymo-orchitis due to Pseudomonas pseudomallei.

We report the first case of epididymo-orchitis caused by Pseudomonas pseudomallei. The diagnosis was made by isolation of the organism from testicle pus and urine. Treatment was successful with chloramphenicol and co-trimoxazole.

Adult↗