Antigens In Lymph Nodes Research Articles

Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates

Antigen accumulation in lymph nodes (LNs) is critical for vaccine efficacy, but understanding of vaccine biodistribution in humans or large animals remains limited. Using the rhesus macaque model, we employed a combination of positron emission tomography (PET) and fluorescence imaging to characterize the whole-animal to tissue-level biodistribution of a subunit vaccine comprised of an HIV envelope trimer protein nanoparticle (trimer-NP) and lipid-conjugated CpG adjuvant (amph-CpG). Following immunization in the thigh, PET imaging revealed vaccine uptake primarily in inguinal and iliac LNs, reaching distances up to 17 cm away from the injection site. Within LNs, trimer-NPs exhibited striking accumulation on the periphery of follicular dendritic cell (FDC) networks in B cell follicles. Comparative imaging of soluble Env trimers (not presented on nanoparticles) in naïve or previously-immunized animals revealed diffuse deposition of trimer antigens in LNs following primary immunization, but concentration on FDCs in pre-immunized animals with high levels of trimer-specific IgG. These data demonstrate the capacity of nanoparticle or “albumin hitchhiking” technologies to concentrate vaccines in genitourinary tract-draining LNs, which may be valuable for promoting mucosal immunity.

Presentation of Autoantigen in Peripheral Lymph Nodes Is Sufficient for Priming Autoreactive CD8+ T Cells.

Peripheral tolerance is an important mechanism by which the immune system can guarantee a second line of defense against autoreactive T and B cells. One autoimmune disease that is related to a break of peripheral tolerance is diabetes mellitus type 1. Using the RIP-GP mouse model, we analyzed the role of the spleen and lymph nodes (LNs) in priming CD8+ T cells and breaking peripheral tolerance. We found that diabetes developed in splenectomized mice infected with the lymphocytic choriomeningitis virus (LCMV), a finding showing that the spleen was not necessary in generating autoimmunity. By contrast, the absence of LNs prevented the priming of LCMV-specific CD8+ T cells, and diabetes did not develop in these mice. Additionally, we found that dendritic cells are responsible for the distribution of virus in secondary lymphoid organs, when LCMV was administered intravenously. Preventing this distribution with the sphingosine-1-phosphate receptor antagonist FTY720 inhibits the transport of antigen to peripheral LNs and consequently prevented the onset of diabetes. However, in case of subcutaneous infection, administration of FTY720 could not inhibit the onset of diabetes because the viral antigen is already presented in the peripheral LNs. These findings demonstrate the importance of preventing the presence of antigen in LNs for maintaining tolerance.

Distribution of CD45RO⁺ T and CD45RA⁺ T Cells in Peripheral Blood of Patients with Peripheral T Cell Lymphoma

To investigate the clinical significance of memory T cells (CD45RO⁺ T) and the initial T cells (CD45RA⁺ T) distribution in peripheral blood of patients with peripheral T-cell lymphoma (PTCL). A total of 27 patients diagnosed as PTCL in our hospital from February 2010 to February 2014 were collected in this study; whereas 30 healthy people were enrolled as control. The distribution of CD45RO⁺ T and CD45RA⁺ T cells were detected seperately in each group, and the results were analysed further. The expression of T cell antigens in lymphnodes of PTCL patients were diverse: the CD4⁺ T cells were the main immune phenotype, while the B cell-related antigen was not expressed. The CD4⁺/CD8⁺, CD4⁺ CD45RO⁺ T in the peripheral blood of PTCL patients were significantly lower than that in normal group (P < 0.05); while the CD4, CD45RA⁺ T, CD8⁺ CD45RA⁺ T and CD8⁺ CD45RO⁺ T were significantly higher than that in normal group (P < 0.05). The patients in stage I/II had higher CD4⁺/CD8⁺, CD4⁺ CD45RO⁺ T than those in stage III/IV (P < 0.05), whereas the CD4⁺ CD45RA⁺ T, CD8⁺ CD45RA⁺ T and CD8⁺ CD45RO⁺ T were significantly lower than those in the stage III/IV patients (P < 0.05). The distributions of CD45RA⁺ T and CD45RO⁺ T in PTCL patients are quite different, and the corresponding treatment might be adopted according to the different distribution of these cells, so as to improve the diagnosis and prognosis of PTCL.

T cell priming in vivo: a major role for B cells in presenting antigen to T cells in lymph nodes.

Previous studies have shown that lymph node (LN) T cells from mice given repeated injections of anti-mu antisera from birth (mu sm) fail to mount secondary T proliferative responses to antigen in vitro after s.c. priming in vivo. This finding raised the possibility that priming of T cells in LN depends on the presence of B cells, Ig+ B lymphocytes being absent in mu sm. In support of this idea, the present paper shows that the priming defect in LN of mu sm can be largely overcome by injecting B cell populations s.c. 1 day before s.c. priming with antigen. Restoration of LN priming was observed with s.c. injection of highly purified populations of small B cells but not with heat-killed or lightly irradiated B cells. Homing studies indicated that approximately 10% of s.c.-injected B cells reached the draining LN. In other studies, irradiated mice injected i.v. with purified T cells manifested poor priming in LN after s.c. injection of antigen. It was reasoned that the LN priming defect in this situation reflected the lack of B cells in irradiated mice, B cells being highly radiosensitive. In support of this notion, it was found that s.c. injection of B cells into irradiated recipients of T cells led to high priming of T cells in LN after s.c. injection of antigen. Although T cells exposed to antigen in B-depleted LN of mu sm and irradiated mice gave negligible T proliferative responses in vitro, low but significant levels of primed T helper function were detected in a sensitive T helper assay in vivo. In light of this finding, our working hypothesis is that the initial induction of T cells to antigen in LN is controlled by resident dendritic cells (or other non-B antigen-presenting cells), the main role of B cells being to control the clonal expansion of activated T cells.

New lymphocyte antigen system (Lna) controlled by the Ir region of the mouse H-2 complex.

A new system of lymphocyte alloantigens in mice is described. This Lna (lymph-node antigen) system is associated with the Ir region of the H-2 (histocompatibility-2) gene complex. It has the following distinctive characteristics: (1) The gene or genes controlling these antigens has been mapped in the Ir (immune response) region between H-2K and Ss-Slp. (2) The antigens are most readily detectable on lymph-node cells, although they are also expressed on peripheral blood lymphocytes, splenic lymphocytes, and thymocytes. (3) Cytotoxicity against only about half of lymph-node cells is consistently observed. (4) Cytotoxic antibody titers against these antigens are strikingly high-more than 2000 by (51)Cr-release and up to 100,000 in the microcytotoxic test. (5) At least two, probably allelic, forms of the antigen(s) have been defined, one associated with the H-2(k) haplotype and one with the H-2(a) haplotype. (6) Antisera against Lna contain multiple antibody specificities that can be fractionated by absorption either with certain recombinants or with other H-2 halotypes that have crossreactive antigens. The antisera against Lna may be of value for definition and characterization of the products of the Ir and MLR (mixed lymphocyte reaction stimulatory) genes associated with the H-2 complex.