Interleukin-2 (IL-2), originally described as a growth factor required for sustained proliferation of T cells in vitro is a glycoprotein hormone of known structure which appears to be important for the generation of immune responses in vivo. As well as T lymphocytes, B lymphocytes and large granular lymphocytes with natural killer activity (NK cells) can also respond to IL-2. The action of IL-2 seemed to be limited specifically to lymphocytes, however, and the term 'T-lymphocytotrophic hormone' was used. Here we provide evidence that human monocytes display a substantially increased cytotoxic activity as a direct and rapid response to human recombinant IL-2 but not to human recombinant glycosylated interferon-gamma (IFN-gamma) or lipopolysaccharide. Our results reveal a previously unknown function of IL-2 and suggest its possible involvement in monocyte-T cell interactions.

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This review gives an overview of two main suppressor circuits. In its complete form, the first circuit form has an early acting Ts-inducer that behaves like a T-helper cell for the production of idiotype-directed Ts-transducer or antigen-directed Ts-effector cells. In this circuit, the T-suppressor effector cell (Ts-eff) produces antigen-specific T-suppressor factor (TsF). This has a mode of action through the T-acceptor cell (T-acc), a cell that requires immunization, but not specific immunization, for its production. This cell, when armed with TsF-eff and then triggered with antigen and I-J, releases nonspecific TsF that blocks the passive transfer of contact sensitivity. It also blocks the production of IL-2. The biological significance of the complexities of this circuit is discussed in relation to the control of unresponsiveness and the handling infection and antigenic variation of microorganisms. The second set of suppressor cells, T suppressor afferent cells, inhibits only when given early in the immune response but differs from the Ts-inducer by lacking an obligatory mode of action through the Ts-eff/T-acc circuit. In general, the antigen-specific T-helper and T-suppressor factors have a two-chain disulfide-bonded structure. One chain carries the antigen-binding site and the other chain MHC-related determinants. Both chains are required for biological activity, and the genetic restriction in this complementation implies that the antigen-binding chain has a recognition site for MHC determinant(s). The generalization can be made that the MHC-related determinants carried by the factors and the genetic restriction in their induction, in their action, and in the interchain complementation between their separated chains all map to the same region of the genome. This is intelligible on the assumption that the T-cell receptor on the cell that produces the factor has a recognition site for antigen and MHC determinants and that the antigen-binding chain of secreted factor has the same properties.

T cell suppression of contact sensitivity in the mouse II. The role of soluble suppressor factor and its interaction with macrophagesContact sensitivity in the mouse is assessed by the increase of ear thickness 24 hours after challenge with antigen and can be passively transferred by T cells in the lymph nodes and spleen of immunized mice. The lymph node cells of mice pretreated with picrylsulfonic acid specifically depress the passive transfer of contact sensitivity to picryl chloride by immune cells."Suppressor" lymph node cells from mice injected with picrylsulfonic acid (-6 days) and painted with picryl chloride (-1 day) were incubated in vitro for 48 hours. Immune lymph node cells incubated in these supernatants have reduced ability to transfer contact sensitivity. This suppression is specific and passive transfer of contact sensitivity to 4-ethoxymethylene-2-phenyloxazolone is unaffected by incubation of immune cells in supernatant. Control supernatants from the cells of mice which did not receive picrylsulfonic acid or were not painted shortly before harvesting were inactive.The suppressor activity is absorbed by peritoneal exudate cells and these then acquire the ability to suppress passive transfer-"arming for suppression". Normal and immune lymph node cells, and spleen cells do not become inhibitory under similar conditions.The suppressor activity of suppressor supernatants (which contain 10 % fetal calf serum) withstands freeze drying, heating at 56 OC and trypsin. Its production is T dependent and is abolished by treatment with anti-@ serum and complement. The hypothesis is put forward that the active factor in suppressor supernatants is a specific T cell product either free or combined with antigen.

Ptak and Askenase showed that both alphabeta and gammadelta cells are required for transfer of contact sensitivity (CS). This study confirms that day 4 immune cells depleted of gammadelta cells fail to transfer CS to trinitrochlorobenzene (TNP-Cl) systemically and demonstrates that administration of anti-gammadelta monoclonal antibodies (mAb) in vivo abolishes the CS reaction. Moreover, gammadelta cells accumulate at the antigen challenge site: these cells have the unusual phenotype CD8alpha+, CD8beta-, IL-4 R+ which we suggest is due to their state of activation. Following immunization with contact sensitizer on the skin, the absolute number of gammadelta cells increases in the regional lymph nodes with a peak at 4 days. Of the gammadelta cells, 80 %, both in the lymph nodes of TNP-Cl-immune mice and accumulating at the antigen challenge site are Vgamma3+. The gammadelta cells expressing Vgamma3, which is characteristic of dendritic epithelial T cells (DETC), obtained 4 days after sensitization, proliferate in response to interleukin (IL)-7, but only poorly to IL-2 and IL-4. They also respond to concanavalin A and immobilized anti-gammadelta mAb, but not to haptens or heat-shocked syngeneic spleen cells. Furthermore, injection of mice with mAb to IL-7 inhibits accumulation of Vgamma3+ cells both in the lymph nodes after skin sensitization and at the antigen-challenge site. Altogether, these results strongly support the view that DETC are related to, or the original source of, the gammadelta cells found in the lymph node after skin sensitization and at the site of challenge, and that IL-7 is implicated in these phenomena.

We have previously reported that T lymphocytes proliferating in vitro to the hapten trinitrochlorobenzene (TNCB) exhibit a very restricted V beta gene usage and response to TNCB is limited to T-cell receptors (TCR) composed of V beta 8.2 in combination with V alpha 3.2, V alpha 8 and V alpha 10. This paper investigates the role played by T lymphocytes expressing the V beta 8.2 gene segment in the contact sensitivity (CS) reaction to TNCB in the intact mouse and in its passive transfer into naive recipient mice. Mice injected with monoclonal antibodies to V beta 8 are unable to develop CS upon immunization with TNCB and 4-day TNCB-immune lymph node cells from mice that had been depleted in vivo or in vitro of V beta 8+ T lymphocytes fail to transfer CS. However, when separated V beta 8+ and V beta 8- cells were used for passive transfer, it was found that V beta 8+ T lymphocytes failed to transfer CS when given alone to recipient mice and a V beta 8- population was absolutely required. Further analysis revealed that within the V beta 8- population, T lymphocytes expressing the gamma delta TCR were fundamental to allow transfer of the CS reaction. These gamma delta cells were found to be antigen non-specific, genetically unrestricted and to rearrange the V gamma 3 gene segment. This indicates that transfer of the CS reaction requires cross-talk between V beta 8+ and gamma delta+ T lymphocytes, thus confirming our previous results obtained using TNCB-specific T-cell lines. Time-course experiments showed that V beta 8+ lymphocytes taken 4-24 days after immunization with TNCB were able to proliferate and produce interleukin-2 (IL-2) in response to the specific antigen in vitro. Similar time-course experiments were then undertaken using the passive transfer of the CS reaction system. The results obtained confirm that TNCB-specific V beta 8+ T lymphocytes are present in the lymph nodes of immunized mice from day 4 to day 24, and reveal that gamma delta+ T lymphocytes are active for a very short period of time, i.e. days 4 and 5 after immunization. In fact, TNCB-specific V beta 8+ cells are able to transfer CS when taken 4-24 days after immunization, providing the accompanying V beta 8- or gamma delta+ T lymphocyte are obtained 4 days after immunization. In contrast, injection of V beta 8+ T lymphocytes together with V beta 8- or gamma delta+ T lymphocytes that had been taken 2 or 6 days after immunization, failed to transfer significant CS into recipient mice. Taken together, our results confirm that cross-talk between V beta 8+ and gamma delta+ T lymphocytes is necessary for full development of the CS reaction and may explain why the CS reaction in the intact mouse lasts up to 21 days after immunization while the ability of immune lymph node cells to transfer CS is limited to days 4 and 5 after immunization.

The reactivity of peripheral blood lymphocytes from patients with advanced malignancy was assessed by mitogen-induced stimulation of protein synthesis as measured by 3H-leucine incorporation. It was confirmed that the lymphocyte response of patients was depressed. Furthermore, the lymphocytes of 15 out of 27 cancer patients, selected because of their low responses, inhibited the reactivity of normal lymphocytes in co-cultures. The lymphocytes from one patient with Hodgkin's disease were also inhibitory. In contrast, lymphocytes from healthy subjects, patients with chronic lymphocytic leukaemia, lymphosarcoma or multiple myeloma caused no suppression. Experiments with purified cell populations from patients with carcinoma indicated that purified T cells responded to mitogens while unseparated lymphocytes failed to respond and that the inhibitory activity was due to adherent cells, presumably monocytes. There was no evidence for B-cell-mediated suppression. However, in two cases inhibition was caused by isolated T cells of the patients and not by adherent cells. These experiments suggested that one mechanism for the depression of cell-mediated immunity seen in patients with advanced cancer may be the nonspecific suppresssion of certain T-cell functions by circulating monocytes.