Suppression of Moloney sarcoma virus immunity following sensitization with attenuated virus.
Murine sarcoma virus (Moloney strain) (MSV-M)-induced tumors are unusual in that they regularly appear less than 2 weeks after virus inoculation, progress for 1 to 2 weeks, and are rejected by normal adult BALB/c mice. Rejectio leaves the animals immune to tumor induction. In the present study, presensitization of normal adult BALB/c mice with attenuated MSV-M resulted in an altered pattern of tumor immunity. Injection of active MSV-M into the presensitized animals resulted in tumor induction and rejection similar to that observed in normal animals, but rejection failed to produce protection against the secondary inoculation with MSV-M. After the second inoculation with active MSV-M, tumors appeared and progressed but ultimately were rejected. Over 80% of the mice died, 25% after the primary challenge and the remainder after the secondary challenge. At death, all mice had histological evidence of leukemia which was the probable cause of death. The animals that died following the secondary challenge also had evidence of disseminated MSV-M. Solid tumor nodules were found in skeletal muscle distant from the original site of inoculation, and active MSV-M was isolated from spleen and lungs. The possibility that the results were produced by specific suppression of MSV-Moloney leukemia virus immunity is discussed. (+info)
Prolonged eosinophil accumulation in allergic lung interstitium of ICAM-2 deficient mice results in extended hyperresponsiveness.
ICAM-2-deficient mice exhibit prolonged accumulation of eosinophils in lung interstitium concomitant with a delayed increase in eosinophil numbers in the airway lumen during the development of allergic lung inflammation. The ICAM-2-dependent increased and prolonged accumulation of eosinophils in lung interstitium results in prolonged, heightened airway hyperresponsiveness. These findings reveal an essential role for ICAM-2 in the development of the inflammatory and respiratory components of allergic lung disease. This phenotype is caused by the lack of ICAM-2 expression on non-hematopoietic cells. ICAM-2 deficiency on endothelial cells causes reduced eosinophil transmigration in vitro. ICAM-2 is not essential for lymphocyte homing or the development of leukocytes, with the exception of megakaryocyte progenitors, which are significantly reduced. (+info)
Analysis of V(H)-D-J(H) gene transcripts in B cells infiltrating the salivary glands and lymph node tissues of patients with Sjogren's syndrome.
OBJECTIVE: In patients with Sjogren's syndrome (SS), B lymphocytes have been found to infiltrate salivary glands, resulting in sialadenitis and keratoconjunctivitis. The disease is frequently associated with benign and neoplastic lymphoproliferation. The present study was undertaken to investigate whether clonal B cell expansion takes place in lymphocytic infiltrations of salivary glands under (auto- [?]) antigen stimulation, by analyzing in more detail the variable part (V(H)-D-J(H)) of the immunoglobulin heavy chain genes expressed in these B cells. METHODS: Biopsies of the labial salivary glands and lymph nodes were performed on 2 female patients with SS. The Ig gene rearrangements in these tissues were amplified by reverse transcriptase-polymerase chain reaction using specific primers. RESULTS: A total of 94 V(H)-D-J(H) transcripts were cloned and sequenced. Our data suggest a polyclonal origin of the B cell infiltrates. In 92 of the transcripts, V(H) genes were modified by somatic mutation. Further analysis showed counterselection for replacement mutations within the framework regions, suggesting that those B cells were stimulated and selected for functional expression of a surface Ig. In labial salivary glands from both patients, clonally related B cells became evident. Members of 1 particular clone were found in both the lip and lymph node material. CONCLUSION: These data provide evidence, on the nucleotide sequence level, that an antigen-triggered clonal B cell expansion takes place in the salivary glands of patients with SS who do not have histologic evidence of developing lymphoma. It may be speculated that those B cell clones expand during disease progression, resulting in lymphomagenesis. (+info)
T-cell lymphoma in a savanna monkey (Cercopithecus aethiops) probably related to simian T-cell leukemia virus infection.
Lymphoma was seen in an 11-year-old female savanna monkey (Ceropithecus aethiops). The superficial inguinal and visceral lymph nodes were markedly enlarged, and their architecture was completely effaced by neoplastic cells. The neoplastic cells, which were highly pleomorphic, resembled those in adult T-cell lymphoma-leukemia in humans. Ultrastructurally the neoplastic cells were characterized by nuclear irregularity and clustered dense bodies, and almost all cells showed positivity for CD3. The animal had been reared with her family, and her mother and 2 brothers had antibodies reactive to human T-cell leukemia virus. This virus serologically cross-reacts with simian T-cell leukemia virus, which may be the causative agent of the present neoplasm. (+info)
Lymphadenitis due to nontuberculous mycobacteria in children: presentation and response to therapy.
The most common manifestation of infection due to nontuberculous mycobacteria (NTM) in children is cervical lymphadenitis in an otherwise healthy patient. We identified and reviewed 19 cases of proven or presumptive lymphadenitis due to NTM seen at our hospital over the course of 13 months. Nine patients underwent initial surgical excision of involved lymph nodes. Ten children did not have involved lymph nodes excised initially and were treated with macrolide-containing antibiotic regimens. Of these patients, five required subsequent surgical excision and five were cured with combination chemotherapy. Six patients underwent radiographic imaging of the head and neck that revealed asymmetrical adenopathy with ring-enhancing masses but minimal inflammatory stranding of the subcutaneous fat, a finding that may distinguish adenitis caused by NTM from staphylococcal and streptococcal adenitis. Our data suggest that if surgical excision is not considered feasible, antimicrobial therapy for adenitis due to NTM may be beneficial for some patients. (+info)
Detection of occult lymph node metastases in esophageal cancer by minimally invasive staging combined with molecular diagnostic techniques.
BACKGROUND AND OBJECTIVES: Lymph node metastases are the most important prognostic factor in patients with esophageal cancer. Histologic examination misses micrometastases in up to 20% of lymph nodes evaluated. In addition, non-invasive imaging modalities are not sensitive enough to detect small lymph nodes metastases. The objective of this study was to investigate the use of reverse transcriptase-polymerase chain reaction (RT-PCR) of messenger RNA (mRNA) for carcinoembryonic antigen (CEA) to increase the detection of micrometastases in lymph nodes from patients with esophageal cancer. METHODS: RT-PCR of CEA mRNA was performed in lymph nodes from patients with malignant and benign esophageal disease. Each specimen was examined histopathologically and by RT-PCR and the results were compared. RESULTS: Metastases were present in 29 of 60 (48%) lymph nodes sample by minimally invasive staging from 13 patients with esophageal cancer when examined histopathologically. RT-PCR identified nodal metastases in 46 of these 60 (77%) samples. RT-PCR detected CEA mRNA in all 29 histologically positive samples and in 17 histologically negative lymph nodes. All lymph nodes from patients with benign disease (n = 15) were negative both histopathologically and by RT-PCR. The stage of two patients was reclassified based on the RT-PCR results, which identified lymph node spread undetected histopathologically. Both of these patients developed recurrent disease after resection of the primary tumor. CONCLUSIONS: RT-PCR is more sensitive than histologic examination in the detection of lymph node metastases in esophageal cancer and can lead to diagnosis of a more advanced stage in some patients. The combination of minimally invasive surgical techniques in combination with new molecular diagnostic techniques may improve our ability to stage cancer patients. (+info)
Expanded tumor-reactive CD4+ T-cell responses to human cancers induced by secondary anti-CD3/anti-CD28 activation.
Generation of tumor-reactive T cells in large numbers ex vivo is a requisite step in the adoptive immunotherapy of patients. We examined the immune responses of T cells derived from tumor vaccine-primed lymph nodes activated with anti-CD3 alone and with an anti-CD3/anti-CD28 combination. Nylon wool-purified CD3+ cells were isolated from vaccine-primed lymph nodes obtained from melanoma, renal cell, and head and neck cancer patients. In the absence of antigen-presenting cells, activation with anti-CD3/anti-CD28 greatly enhanced subsequent T-cell expansion in interleukin 2 (>100-fold), compared to anti-CD3 alone. CD4+ T cells were preferentially stimulated. In four of eight patients, we found evidence of CD4+ cellular responses to autologous tumors by cytokine release assays. Positively selected CD4+ cells activated with anti-CD3/anti-CD28 released greater amounts of cytokine (IFN-gamma and granulocyte macrophage colony-stimulating factor) in response to autologous tumors compared to cells activated by anti-CD3 alone. The CD4+ reactivity was MHC class II restricted and appeared to be associated with the expression of class II molecules on the vaccinating tumor cells. The CD4+ T-cell responses to class II-restricted tumor-associated antigens in patients with renal cell cancers represent unique findings. (+info)
Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand.
Among members of the tumor necrosis factor receptor (TNFR) superfamily, 4-1BB, CD27, and glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) share a striking homology in the cytoplasmic domain. Here we report the identification of a new member, activation-inducible TNFR family member (AITR), which belongs to this subfamily, and its ligand. The receptor is expressed in lymph node and peripheral blood leukocytes, and its expression is up-regulated in human peripheral mononuclear cells mainly after stimulation with anti-CD3/CD28 monoclonal antibodies or phorbol 12-myristate 13-acetate/ionomycin. AITR associates with TRAF1 (TNF receptor-associated factor 1), TRAF2, and TRAF3, and induces nuclear factor (NF)-kappaB activation via TRAF2. The ligand for AITR (AITRL) was found to be an undescribed member of the TNF family, which is expressed in endothelial cells. Thus, AITR and AITRL seem to be important for interactions between activated T lymphocytes and endothelial cells. (+info)