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The binding of EPF to lymphocytes stimulates the release of soluble mediators, active in T cell dependent reactions, namely the rosette inhibition test and the adoptive transfer of contact sensitivity. On the basis of their ability to inhibit the delayed type hypersensitivity reaction in this latter assay, they have been classified as suppressor factors. This paper describes the identification of two EPF-induced suppressor factors. Unlike EPF which is neither species-restricted nor strain-restricted, these factors are genetically restricted in their action in the rosette inhibition test EPF-S1 (estimated Mr 14,000) is restricted to the I region of the mouse MHC, while EPF-S2 (estimated Mr 55,000) is restricted to a locus (or loci) outside the MHC. Like other antigen non-specific factors, release of these suppressor factors can be stimulated also by Con A. [ABSTRACT FROM AUTHOR]

The article presents a study related to the regulation of the magnitude of Th2-mediated airway inflammation, through the inducible costimulator (ICOS) expression. It is stated that ICOS is a potential immunotherapeutic target for allergy and asthma, apart from being a crucial regulator of Th2 lymphocyte function. It was concluded that the level of ICOS surface expression, in both mice and humans, regulates the magnitude of the in vivo Th2 response, may be by affecting Th2 differentiation. The background, methodology/principal findings, and conclusion, of the study, are discussed in detail.

Mice were immunized with the cell wall of BCG suspended in an oil-in-saline emulsion, and examined against time for the emergence of T cell-mediated acquired immunity. Evidence is presented that shows that levels of acquired resistance expressed in these animals over the first month following inoculation, and which enabled them to substantially resist an intravenous challenge infection with Mycobaeteriurn tuberculosis, were completely nonspecific in nature, in that they were equally well expressed in normal and T cell-deficient mice, and were present at a time when no protective T cell activity could be passively transferred from the inoculated host. Paradoxically, in contrast, weak but statistically significant protective immunity could be detected in the spleens of CW-immunized mice approximately 3 months after inoculation, at a time when the donor animals were devoid of resistance to rechallenge. Finally, evidence is presented that shows that the CW material, if given subcutaneously, is highly immunogenic for the generation of delayed-type hypersensitivity effector T cells; however, these cells do not themselves contribute to protective immunity. [ABSTRACT FROM AUTHOR]

X-irradiated (250 rads) A mice injected with syngeneic trinitrophenylated spleen cells (Syn-TNP-SC) developed syngeneic delayed-type hypersensitivity (Syn-DTH) after footpad challenge with syngeneic concanavalin A-induced lymphoblasts (Syn-Con A blasts), as indicated by footpad swelling and lymph-node proliferation assays. Genetic analysis with different recombinant strains of mouse revealed that the H-2Dd subregion restricts these immunological activities. A small immunogenic entity was isolated from Syn-TNP-SC extract by gel filtration and affinity chromatography with anti-Dd antibody. X-irradiated A mice injected with this antigen also generated inflammatory responses after challenge with Syn-Con A blasts. Analysis of the data obtained from the gel filtration and the affinity chromatography suggest that the Syn-DTH-stimulating antigen is a fragment of the H-Dd heavy chain with a molecular weight (MW) of 5,000 to 10,000. This fragment does not contain TNP molecules or sugar moieties and neither does it express affinity for antibodies against class 11 products. Ltk- cells transfected with the H-2Dd gene also induced Syn-DTH in X-irradiated A mice, while the parent cells failed to stimulate such a response. Taken together these findings indicate that the selection process in the thymus is not absolute and T cells recognizing self-major histocompatibility complex (MHC) products do migrate from this organ to the periphery of the immune system. The possible biological significance of these autoreactive cells is discussed. [ABSTRACT FROM AUTHOR]

A unidirectional cascade of cell interactions has been described previously that involves at least three distinct populations of suppressor T cells (Ts) that interact in appropriate succession to mediate suppression of delayed hypersensitivity responses to the 4-hydroxy-3-nitrophenylacety1 hapten (NP). The present work focuses on the potential bidirectional effects of one suppressor factor and how it can regulate the homeostatic mechanisms that maintain this suppressor cell cascade. Specifically, the effects of prior administration of mice with a transducer suppressor factor (TsF2) on the generation of NP-specific Ts1 suppressor cells were evaluated. It was observed that the TsF2 given 2-14 days prior to administration of the tolerogen (NP-coupled splenic-adherent cells) interfered with the development of inducer Ts1 suppressor cells. This down-regulation of suppressor cell induction is mediated by a population of cells that have the following characteristics: NP-binding, Lyt-l+2-, L3T4+, I-J+, and Vicia villosa (VV)-adherent T cells (for convenience these cells are termed anti-suppressor cells). Furthermore, there are genetic restrictions (both H-2 and IgH) between TsF2 and host which control the generation of anti-suppressor cells. The results suggest that TsF2 may have a role in homeostatic mechanisms that regulate the NP-specific suppressor cell cascade. The relationship of anti-suppressor and contra-suppressor cells is discussed. [ABSTRACT FROM AUTHOR]

The relative radiosensitivities of precursor (Tsp), activated (Ts) and memory (Tsm) suppressor T cells for delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) were investigated in mice. Spleen cells from CBA mice, primed i.v. with 109 SRBC 3–4 days previously, contain specific Ts cells which substantially impair the induction of DTH to SRBC in normal syngeneic recipients. Exposure of mice to 400 rad irradiation 1 day before the priming completely eliminated the subsequent development of Ts cells. In contrast, 3 days after the priming injection, Ts cell activity in mice is resistant to doses higher than 600 rads. Mice primed 40 days previously with 109 SRBC contain Ts-cell memory which can be readily recalled by i.p. injection of 108 SRBC, The secondary Ts cells which specifically inhibit DTH induction can be demonstrated adoptively in normal recipients. Mice were exposed to various doses of irradiation 40 days after the priming and 1 day before the i.p. injection, Ts memory was significantly reduced by 300 rads and was completely abrogated by 400 rads. The relative radiosensitivities of the three subsets of suppressor T cells are in the order of Tsm = Tsp > Ts. [ABSTRACT FROM AUTHOR]

DTH reactions to sheep erythrocytes (SRBC) and purified protein derivative (PPD) antigens were produced in the pleural cavity in mice. The profiles of the DTH reactions with respect to time course and cellular exudate reactions differed greatly according to the strains of mice. In particular, HY mice that were established in our laboratory displayed prolonged DTH reactions, characterized by macrophage followed by lymphocyte reactions. HY × C3H F1 mice showed a similar tendency. On the other hand, strains such as C3H, BALB/c, DBA/2 and B6 mice showed short-lived and macrophage-predominant DTH reactions. BALB/c nu/nu mice showed no DTH reactions. Characteristic features of the prolonged DTH reactions in HY mice were transferred with sensitized T cells. However, DTH reactions in HY mice treated with cyclophosphamide (CY) terminated in a short period, and mainly consisted of macrophages and polymorphs, although they were greatly enhanced. Such profiles of the reactions could also be transferred with sensitized T cells from CY-treated and SRBC-sensitized mice. Spleen cells taken from CY-treated and SRBC-sensitized HY mice, when injected intravenously into SRBC-sensitized HY mice just prior to challenge, could not interrupt prolonged DTH reactions. These results thus indicated various phenotypes of the DTH reactions in terms of time course and exudate cellular component involved might be carried by the specific effector T cells in each phenotype of the DTH reactions and could be induced using strains of mice and CY. [ABSTRACT FROM AUTHOR]

Relationships among T-cell mediated cytotoxicity, tuberculin type hypersensitivity, Jones-Mote type hypersensitivity and activation of helper T cells were studied in AKR mice by means of target cell destruction (51Cr-release), footpad reaction, migration inhibition test and antibody production against the trinitrophenyl group. (1) Immunization with chicken red blood cells (CRBC) in saline, Freund's incomplete (FIA) or complete adjuvant (FCA) and fixed-CRBC (FRBC) in FIA or FCA induced delayed hypersensitivity as demonstrated by footpad swelling. (2) Migration inhibition was positive in the group immunized with CRBC in saline or FCA, or FRBC in FCA, but negative in those immunized with CRBC or FRBC in FIA. This may suggest that the former has to be assigned to tuberculin type and the latter to Jones-Mote type. (3) T-cell mediated cytotoxicity by immune spleen cells was detected only in mice immunized with CRBC in saline, (4) Pre-treatment with cyclophosphamide augmented delayed footpad reaction in mice immunized with CRBC in saline, but suppressed cytotoxic activity. (5) FRBC in saline scarcely induced delayed footpad reaction and cytotoxic activity, whereas they activated helper function efficiently. Thus, four types of immunological phenomena, attributable to the functions of T cells, may depend upon distinct subpopulations of differentiated T cells which are raised by different methods of immunization. [ABSTRACT FROM AUTHOR]

Relationships among tuberculin type hypersensitivity, Jones-Mote type hypersensitivity and activation of helper T cells were studied in AKR mice by means of footpad reaction, migration inhibition test and antibody production against the trinitrophenyl group. (1) Immunization with SRBC in saline, Freund's incomplete adjuvant (FIA) or complete adjuvant (FCA) and fixed-SRBC (FRBC) in FIAor FCA-induced delayed hypersensitivity as demonstrated by footpad swelling. (2) Migration inhibition was positive in the groups immunized with SRBC or FRBC in FCA, but negative in those immunized with SRBC in saline or FIA or FRBC in FIA. This may suggest that the former has to be assigned to tuberculin type and the latter to Jones-Mote type. (3) Both pre-treatment with BCG and with cyclophosphamide (CY) augmented delayed footpad reaction in the mice immunized with SRBC in saline. However, migration inhibition was positive only in the group pre-treated with BCG. BCG may convert the reaction from Jones-Mote type to tuberculin type, while CY may augment the reaction of Jones-Mote type. (4) FRBC in saline scarcely induced delayed footpad reaction, whereas they activated helper function efficiently. Thus, three types of immunological phenomena attributable to the functions of T cells may depend upon distinct subpopulations of differentiated T cells which are raised by different methods of immunization. [ABSTRACT FROM AUTHOR]