Though immune outcome is known to be determined by which helper T cell response predominates, no local mechanism has yet been established which can explain how the neuronal system may control this. It is possible that the nervous system releases neuropeptides at specific local sites of infection or challenge, which triggers lymphocytes at those points to release specific cytokine profiles. These may then influence the direction of the Th1/Th2 response and therefore immune outcome. The aim of this study was to evaluate whether and if so how neuropeptides influence cytokine production by lymphocytes, especially T cells. We investigated the effects of neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal peptide (VIP) on the production of interferon-γ (IFN-γ) and interleukin-4 (IL-4) by stimulating nonadherent splenocytes and helper T cell clones with antigens in vitro in the presence or absence of these peptides. NPY greatly enhanced IL-4 production and inhibited IFN-γ. CGRP inhibited IFN-γ production markedly in a dose-dependent manner, but had no effects on IL-4 production. SP and VIP had no effects on IFN-γ production, but SP enhanced and VIP suppressed IL-4 production slightly but consistently. Therefore neuropeptides can influence cytokine production. This opens the door to speculations that these specific cytokine profiles might play a part in influencing the direction of the consequent Th1/Th2 cascade and immune outcome and possibly the pathogenesis of immune-related diseases.

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We previously reported that the nude mouse-derived splenic T cell clone N-9F exhibits a proliferative response when cultured on thymic stromal cells. This N-9F proliferation is mediated by direct cell-to-cell interactions between T and thymic stromal cells. A thymic epithelial cell clone, SL10.3, also supports N-9F growth. To identify the molecule involved in T cell development in the thymus, we established mAb specific to the N-9F clone. One of these mAb, QR6.6, was found to inhibit the N-9F proliferative response on SL10.3. QR6.6-positive cells were detected in thymus but not in other lymphoid organs such as bone marrow, lymph nodes, or spleen. QR6.6-positive cells accounted for 3 to 5% of the cells in adult thymuses whereas higher percentages were found in neonatal (10-20%) and fetal thymuses (70% at E17 and 10-20% at E15). The positive cells were primarily CD4-8- thymocytes in fetuses and CD4-8- to CD4+8+ thymocytes in adults. The QR6.6 mAb precipitates a 100 kDa molecule from the N-9F clone. The addition of the mAb to fetal thymus organ culture reduces the recovery of cells at culture day 4. It was also found that the mAb inhibits fetal thymocyte proliferation on the SL10.3 thymic epithelial cell line. These results suggest that the 100 kDa molecule detected by the QR6.6 mAb may play a crucial role in the early stage of thymocyte development.

Experiments are described for T-independent polyclonal activation of B cells in vitro by the immunoglobulin binding substance (IBS) from the granary weevil. The affinity-chromatographically purified IBS was used. IBS is a heat-, alkali- and acid-stable glucopeptide which is characterized by non-specific immunoglobulin binding to the Fab fragment. The purified IBS consists of three polymer homologues whose molecular weights are 12-14,000, 25-30,000 and more than 150,000 Da. IBS did not stimulate DNA synthesis by murine T cells, macrophages or plasma cells whereas it did stimulate that by mature B cells without any help from T cells or macrophages. IBS also stimulated both in vitro IgG production by spleen cells and in vitro sensitization of spleen cells by sheep red cells (SRBC). IBS was found to stimulate DNA synthesis by B cells mediated by binding to surface immunoglobulins of B cells. IBS is thought to be a useful amplifier for inducing human hybridomas and a valuable tool for examining mature B cells, both diagnostically and experimentally.

We recently reported that a unique B cell clone (B19-1d), specific for a cross-reactive idiotype (CRI) on MOPC104E myeloma protein (M104E), enhances Igh-restricted CRI+ antibody production. In this paper, we report the nucleotide sequences of Immunoglobulin heavy chain variable regions (VH) of both M 104E and B19-1d-derived hybridoma (HB19) antibodies. The sequence data revealed that both belong to the J558 germ line VH gene subfamily. Strikingly, not only the VH region, but also the leader sequences of M104E and HB19 are very similar to each other at 88 % (VH) and 91 % (leader) homology, but they use different D and J segments. The VH region sequence similarity is highest among the germ line VH gene sequences of the BALB/c J558 subfamily so far screened. Southern hybridization data, using 5'-noncoding regions of either M104E or HB19 genomic VH gene clones as probes, revealed that both VH genes are conserved in the M104E CRI producer strains of mice. Moreover, these probes show the restriction length polymorphism pattern of mouse VH genes in various strains. That the HB19 VH gene locates to the 5' upper arm of the M104E VH gene on the chromosome was suggested by Southern blot hybridization.Immunoglobulin VH gene restriction of idiotypic and antiidiotypic B-B cellular interaction is discussed from a molecular point of view.Cellular interactions through idiotopes on antigen receptors play an important role in the repertoire generation of lymphocytes. An analysis of these interactions provides useful information for understanding the mechanisms for both the regulation and diversification of the immune system (reviewed in 3, 15). In addition to the antibody-producing function of B lymphocytes, several reports have shown that