Search

In different murine systems, delayed-type hypersensitivity (DTH) swelling responses at 24–48 hr after antigen challenge were preceeded by an early 2-hr swelling response. The 24-hr DTH response is thought to depend on this early (DTH-initiating) hypersensitivity response. In this paper we show that in the syngeneic DBA/2-SL2 routine turnout system only an early 2-hr swelling response can be evoked. This early hypersensitivity response was tumour specific and serotonin dependent. The early hypersensitivity response in contact hypersensitivity has been ascribed to antigen-specific T-cell factors. To test whether similar T-cell factors were involved in the early hypersensitivity response in this syngencic turnout system, we have transferred lymph node, spleen lymphocytes and scram from immunized mice into naive recipients. The serum was fractionated in two fractions, a 50,000–80,000 MW fraction, and a 120,000–190,000 MW fraction. In recipients of lymphocytes, total serum and the 50,000–80,000 MW fraction of the serum, an early hypersensitivity response can be evoked. So, these data suggest the involvement of specific T-cell factors in the development of an early hypersensitivity response against syngeneic tumour cells. Despite the development of an early (DTH initiating) hypersensitivity swelling response these immunized animals cannot develop a classical 24-hr swelling response. This absence of the 24-hr response in the presence of the 2-hr response is discussed in relation to the frequently observed immune suppression in tumour-bearing mice. [ABSTRACT FROM AUTHOR]

This paper investigates desensitization in vitro, e.g. the inhibition of the transfer of contact sensitivity to picryl chloride by incubation of the passive transfer population with picrylated spleen cells. It asks whether desensitization is based on the same T-suppressor circuit which is responsible for the inhibition of passive transfer by antigen-specific T-suppressor factor (TsF). In this circuit, the T-suppressor cell which acts at the efferent stage (Ts-eff) makes TsF. This TsF depresses contact sensitivity indirectly by arming a T-acceptor cell (Tacc). The armed Tacc, when exposed to antigen (picrylated spleen cells), liberates a non-specific inhibitor which blocks the transfer of contact sensitivity. The three elements of this T-suppressor circuit occur in nylon wool-purified T cells prepared from the lymph nodes and spleens of mice four days after immunization with picryl chloride. This population transfers contact sensitivity and can be desensitized in vitro. It contains Ts-eff which can be isolated by panning (adherence) on picrylated albumin and detected by their ability to inhibit passive transfer. The 24 hr supernatant of cultures of these cells contains TsF. Finally the population contains Tacc which appear in the spleen 2 days after immunization and virtually disappear by 10 days. Further experiments demonstrated that the Ts-eff and the Tacc were not merely present but actually required for desensitization in vitro. Immune cells depleted of both Ts-eff (by panning on picrylated albumin) and Tacc (by arming with anti-oxazolone TsF and panning on oxazolonated albumin) cannot be desensitized. To restore desensitization both Ts-eff and Tacc must be added back. The Ts-eff were characterized as cyclophosphamide resistant, adult thymectomy sensitive cells (Cyr, ATx5), which adhered to antigen and were produced only by specific immunization. The Tacc were characterized as CF5, ATx5 cells which adhered to antigen only after arming with antigen-specific T-suppressor factor and were produced after immunization with an unrelated contact sensitizer, 'oxazolone'. It was concluded that desensitization in vitro was due to the interaction of two distinct T cells: the T-suppressor cell which acts at the efferent stage of the contact sensitivity reaction and the T-acceptor cell which becomes armed with the specific T-suppressor factor produced by the Ts-eff. [ABSTRACT FROM AUTHOR]

Regulatory T cells are induced by oral administration of an antigen, but the physiological requirements and localization of the inductive sites are largely unknown. Using an adoptive transfer system of cells transgenic for ovalbumin T-cell receptor (OVA TCR tg), we found that antigen-specific CD4+ T cells were activated in the liver-draining celiac lymph node (CLN) shortly after ovalbumin feeding, and that a significantly higher proportion of the T cells in the CLN developed into the putative regulatory phenotype [co-expressing CD25 with the glucocortico-induced tumour necrosis factor (TNF) receptor family related gene (GITR), cytotoxic T-lymphocyte antigen (CTLA)-4 and CD103] than in Peyer's patches, the mesenteric and peripheral lymph nodes and the spleen. In addition, a particularly high level of expression of CD103 on the OVA-specific T cells in the CLN may favour homing to the epithelium of the intestine. While equally suppressive, OVA tg T cells isolated from the CLN of OVA-fed DO11·10 mice were less dependent on transforming growth factor (TGF)-β for suppression than cells isolated from the peripheral and mesenteric lymph nodes, which indicates the involvement of an additional suppressive mechanism. The expression of FoxP3 was not up-regulated in any of the lymph node compartments studied. Our phenotypic and functional findings suggest that the induction of regulatory T cells in the CLN may be relevant in the control of the immune response to dietary antigens. [ABSTRACT FROM AUTHOR]

Antigen-specific T-helper cells for IgA responses arise in Peyer's patches (PP) following their immunization by subserosal injection of keyhole limpet haemocyanin (KLH). These are of the W3/25 phenotype and the W3/25 receptor is shown here to be involved in their helper function. These cells originate in PP and migrate via mesenteric lymph nodes (MLN) to thoracic duct lymph, although the MLN appear to be unnecessary for the induction or maturation of antigen-specific helper cells collected in thoracic duct lymph after intra-Peyer's patch (i.p.p.) immunization. KLH-specific helper cells can be detected subsequently in the intraepithelial lymphocyte population and also among lamina propria lymphocytes. The helper cells also relocate to PP distant to their site of origin where they are retained only when antigen is present. While i.p.p. immunization is an efficient route for the induction of IgA helper cells in gut-associated lymphoid tissue, it differs from oral immunization in that concomitant induction of antigen-specific splenic suppressor cells does not occur, indicating a role for epithelial antigen processing in this phenomenon. [ABSTRACT FROM AUTHOR]

A panel of T-cell clones reactive to the soluble egg antigen (SEA) of Schistosoma mansoni is described. The proliferative responses of the primary immune lymph node (LN) cells and T-cell clones to different schistosome antigen preparations (cercarial extract (CE), live or dead schistosomula, adult worm extract, and soluble egg antigen) were compared. Primary immune LN cells could not distinguish between these schistosome antigen preparations. However, when a total of 22 T-cell clones was analysed, a complex pattern of both stage-specific and common (or cross-reactive) antigen reactivity was observed. These patterns have been grouped into four types: (i) five clones were reactive to all different schisto-some antigen preparations; (ii) two clones were reactive only to SEA, CE and schistosomula; (iii) three clones were reactive only to SEA and cercariae; (iv) twelve clones were reactive to SEA antigen alone. The T-cell clones were identified as Thy-1-positive cells. All the clones were able to respond to exogenous IL-2 after antigenic stimulation. However, there was a variable degree of IL-2 responsiveness when compared with antigen-specific stimulation. Four T clones were selected for further studies on the genetic control of the proliferative response to schistosome antigens. One of the proliferative T clones was restricted by the JA subregion of the major histocompatibility complex (MHC), and the other three clones are restricted by the 1E (ACEα) subregion. [ABSTRACT FROM AUTHOR]

Antigen-specific T helper factor appears in the 24 hr supernatant of lymph node cells taken 4 days after immunization with contact sensitizer. The factor is assayed by its ability to augment the contact sensitivity response induced by haptenized spleen cells. In practice, picrylated or oxazolonated spleen cells are treated with the factor for 1 hr at 4° and 4 × 106 cells are injected into the footpads of recipient mice. Contact sensitivity is assessed 5 days later. The factor first appears 3 days after immunization and its production depends on an Lyt-1+2-, I-A+, I-J- T cell. It is antigen-specific in its action in a criss-cross experiment, and can be absorbed with and eluted from haptenized beads. It bears I-A determinant(s) and the I-A determinant and the antigen binding site(s) occur on the same molecule. The molecular weight is around 60,000. The possible role of T helper factors in the activation of the antigen-presenting cell in the induction stage of the immune response is discussed. [ABSTRACT FROM AUTHOR]

Mice simultaneously injected intravenously and subcutaneously with herpes simplex virus fail to adoptively transfer delayed hypersensitivity (DH) to syngeneic recipients. The transferred lymph node cells also failed to rapidly eliminate infectious herpes from the pinna, despite the presence of cytotoxic T cells in the transferred suspension. Both primary and secondary cytotoxic cell responses in the draining lymph node were unaffected by the inhibition of DH. The lymph nodes from DH tolerized mice also contain lymphocytes capable of undergoing a proliferative response in vitro to herpes antigens. In addition, a neutralizing antibody response with IgG antibodies against herpes are also present in DH tolerized mice. These data suggest a form of split T-cell tolerance in which only DH responses are directly compromised. The implication of these findings for the pathogenesis of herpes simplex virus is discussed. [ABSTRACT FROM AUTHOR]

Details are given of a system for keyhole limpet haemocyanin (KLH)-induced DNA synthesis by murine T lymphocytes in vitro. Lymph node T cells from mice primed with KLH and Bordetella pertussis were stimulated with KLH under the defined conditions, and it was found that such cultured cells exhibited substantial non-specific helper activity. In contrast similarly primed T cells which had not been cultured showed only antigen-specific help. it is concluded that proper account should be taken of nonspecific effects when studying the activity of antigen-specific helper cells in in vitro. [ABSTRACT FROM AUTHOR]

Murine amniotic fluid (MAF), alpha-foeto-protein (AFP) and MAF depleted of AFP by affinity chromatography (MAF-AFP) inhibited the T-cell dependent in vitro proliferative responses of lymph node cells sensitized to a variety of soluble antigens. Variable degrees of inhibition were observed with the different antigens used in the assay. In general, the higher the proliferative response induced by a particular antigen, the less it was inhibited by the three inhibitors. Enhancement of proliferation was not infrequently observed at lower concentrations followed by a dose-dependent inhibition as the concentration of the inhibitor was increased. Usually the order of inhibition was MAF > MAF-AFP ≥ AFP although variations in inhibitory potency were noted between different preparations of AFP and MAF-AFP. The existence of inhibitors in preparations of MAF depleted of AFP raised the question as to whether MAF contains single or multiple inhibitory factors. The most facile explanation is that two inhibitors exist; AFP and the as yet uncharacterized non-AFP suppressor present in MAF-AFP. [ABSTRACT FROM AUTHOR]

The T-cell repertoire to a prominent immunogen of Mycobacterium tuberculosis has been investigated on the assumption that differences in epitope specificity could influence the protective and pathogenic host reactions. Proliferative responses of lymph node and spleen cells to overlapping peptides, spanning the entire sequence of the 16,000 MW protein antigen were analysed in C57BL/10 and B10.BR mice. Following footpad priming and in vitro challenge with homologous peptide, 12 out of the 14 peptides tested were found to be immunogenic. However, only two peptides of residues 31-40 and 71-91 stimulated strong proliferative responses of T cells from mice which had been presensitized with either killed or live M. tuberculosis organisms; another three peptides were only weakly stimulatory. These epitopes have been immunodominant in both H-2b and H-2k mouse strains, indicating the genetically permissive nature of their recognition. Furthermore, both major immunodominant epitopes were found to be species specific for the M. tuberculosis complex and therefore potentially suitable for the early diagnosis of tuberculous infection. [ABSTRACT FROM AUTHOR]

The effects of antigenic stimulation on the expansion of T-cell dependent areas in lymph nodes of mice were studied in relation to the effects on high endothelial venules (HEV) located in this area. Lymph nodes regional to areas of skin that had been treated with solutions of oxazolone were studied at several time-points after stimulation. The following measurements were made relative to lymph nodes of untreated animals: (i) the expansion of the T-cell dependent area in combination with the increase of HEV in this area, as detected by the HEV-specific mAb MECA-325, using morphometric analysis; (ii) the influx of FITC-labelled lymphocytes from the blood into the lymph node by FACS; (iii) the capacity of HEV to bind lymphocytes using an in vitro binding assay. Morphometry showed that T-cell dependent areas increased rapidly after stimulation with oxazolone and although the mean area of MECA-325-positive HEV had also increased, this increase lagged behind the expansion of the T-cell area. Therefore the amount of HEV per T-cell area in an antigen-stimulated lymph node was smaller than in an untreated lymph node and correlated with the percentage of FITC-labelled cells that had entered it. In a lymph node from an oxazolone-treated animal this percentage was decreased to the same order of magnitude as the area of HEV per T-cell area, but the overall binding capacity of HEV was not affected by oxazolone treatment. Antigenic stimulation therefore leads to a rapid expansion of the potential sites of lymphocyte entry into a lymph node, but the efficiency of the HEV does not change. [ABSTRACT FROM AUTHOR]