Serum antibody response and nasal lymphoid tissue (NALT) structure in the absence of IL-4 or IFN-gamma.

Immunization via the nasal route is effective for inducing not only mucosal immunity but also antibody (Ab) response in serum. Nasal lymphoid tissue (NALT) is important for induction of systemic immunity. It remains controversial which T effector cell response is important for serum Ab response after nasal immunization. We investigated serum Ab responses and NALT structures in interleukin (IL)-4 gene targeted (IL-4(-/-)) and interferon (IFN)-gamma gene targeted (IFN-gamma(-/-)) mice. Mice were immunized via nostrils with ovalbumin (OVA) and cholera toxin as adjuvant and serum Ab titers were measured 1 week after final antigen challenge. OVA-specific IgG titers in sera of IL-4(-/-) mice indicated a Th(1) type response, whereas titers in IFN-gamma(-/-) mice and wild-type mice indicated a Th(2) type response. Enhanced serum Ab responses were observed in IL-4(-/-) mice but not IFN-gamma(-/-) mice. OVA-specific Ab-forming cells were detected in the cervical draining lymph nodes but were rare or absent in and around the NALT of all strains of mice. Numbers of OVA-specific Ab-forming cells in cervical lymph nodes were significantly higher in IL-4(-/-) mice than in wild-type and IFN-gamma(-/-) mice. Germinal centers of lymphoid follicles were present in NALT of IL-4(-/-) and other mice. Immunohistochemistry for B and T cell markers revealed that NALT of all mice had approximately the same cellular compositions. Although the absence of IL-4 had no effect on NALT structure, IL-4 may suppress induction of serum Ab responses by nasal immunization.

Expression of tumor necrosis factor ligand superfamily costimulatory molecules CD27L, CD30L, OX40L and 4-1BBL in the heart of patients with acute myocarditis and dilated cardiomyopathy.

BACKGROUND: T-cell-mediated myocardial damage is known to be involved in acute myocarditis and dilated cardiomyopathy. Recently, we found that tumor necrosis factor (TNF) ligand superfamily costimulatory molecules, especially 4-1BBL, played an important role in the myocardial damage of murine acute viral myocarditis. METHODS AND RESULTS: To investigate the roles for CD27L, CD30L, OX40L and 4-1BBL, which belong to TNF ligand superfamily, in the development of acute myocarditis and dilated cardiomyopathy, we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and dilated cardiomyopathy. We also examined expression of the receptors for these molecules, CD27, CD30, OX40 and 4-1BB, which belong to TNF receptor superfamily, on the infiltrating cells. Strong expression of CD27L, CD30L and 4-1BBL and weak to moderate expression of OX40L was found in the cardiac myocytes of patients with acute myocarditis. Moderate expression of CD27L, CD30L and 4-1BBL and weak expression of OX40L was found on the cardiac myocytes of patients with dilated cardiomyopathy. Most of the infiltrating cells expressed CD27, CD30 and 4-1BB and a part of the infiltrating cells expressed OX40. CONCLUSIONS: Our findings suggest that expression of TNF ligand superfamily costimulatory molecules on cardiac myocytes may play a role in the cell-mediated myocardial damage in patients with acute myocarditis and dilated cardiomyopathy as in murine viral myocarditis.

Mature dendritic cells make clusters with T cells in the invasive margin of colorectal carcinoma.

Dendritic cells (DCs) take up tumour-specific antigen and migrate to regional lymph nodes to generate anti-tumour immunity. Although DC infiltration within human tumour tissue has been reported, the subset distribution has not been fully investigated. This study used immunohistochemistry to investigate DC subset distribution in colorectal adenocarcinoma. DCs expressing CD83, which are considered to be mature DCs, were present mainly in the invasive margin of cancer stroma. CD83(+) DCs in the invasive margin formed clusters with lymphocytes, the majority of which were CD45RO(+) T cells. The number of CD4(+) T cells was greater than that of CD8(+) T cells in these DC-lymphocyte clusters. The elongated cytoplasmic processes of CD83(+) DCs engulfed CD4(+) T cells. DCs that express CD1a were located throughout tumour tissue. Although the number of CD1a(+) DCs was almost the same as that of CD83(+) DCs in the invasive margin of cancer stroma, CD1a(+) DCs were mostly scattered and rarely formed clusters with lymphocytes. DCs that expressed both CD1a and CD83 were rare. Moreover, about 20% of lymphocytes in DC-lymphocyte clusters were positive for Ki-67, and CD83(+) DCs were attached to Ki-67(+) cells. CD83(+) DCs were also present in T-cell areas that had a distinctive structure involving the presence of B-cell lymphoid follicles. These results suggest that in the invasive margin of the colorectal cancer stroma, mature CD83(+) DCs form clusters with T cells to promote T-cell activation for the generation of tumour-specific immunity.