Phenotypic and functional characteristics of active suppressor cells against IFN-gamma production in PHA-stimulated cord blood lymphocytes.

Cord blood mononuclear cells (MNC) were defective in their ability to produce interferon-gamma (IFN-gamma) on stimulation with phytohemagglutinin (PHA) or recombinant interleukin 2, whereas cord MNC could induce comparable amounts of IFN-gamma with adult controls on stimulation with a streptococcal preparation, OK-432. Moreover, irradiation of cord MNC with 1,500 rad before PHA stimulation could restore the IFN-gamma production. Kinetic studies indicated that such augmentation of IFN-gamma production by irradiation was evident when cord MNC were irradiated before or by 12 hr of PHA-stimulated culture. But irradiation after 18 hr or more of PHA stimulation did not exert any significant augmentation on IFN-gamma production by cord MNC. It seemed most likely that the ability of IFN-gamma production is already mature at birth, but radiosensitive suppressor effectors on IFN-gamma production are activated within cord MNC at an early stage of PHA stimulation, resulting in poor IFN-gamma production by cord MNC. PHA-induced IFN-gamma production by OKT3+, OKT4+, and OKT8- cord cells were markedly enhanced by irradiation with 1,500 rad before the culture. Coculture experiments disclosed that cord OKT4+ cells, but not OKT4- cells, when prestimulated with PHA for 24 hr, exerted active suppression on PHA-induced IFN-gamma production by adult MNC in a dose-dependent manner. These results suggested that radiosensitive suppressor effectors on IFN-gamma production were induced within the OKT4+ T cell subset of cord MNC on PHA stimulation.

Sequential expression of T cell activation (Tac) antigen and Ia determinants on circulating human T cells after immunization with tetanus toxoid.

Recent studies have indicated that a monoclonal antibody, termed anti-Tac, may recognize the receptor sites or closely associated structures for interleukin 2 on activated human T cells. The Tac antigen, definable by anti-Tac antibody and usually found on mitogen- or alloantigen-stimulated T cells, was not expressed to any appreciable extent on normal circulating T cells. In the present study, we showed that an increase in circulating T cells expressing Tac antigen as well as Ia determinants occurred in normal individuals after immunization with tetanus toxoid. The expression of Tac antigen and Ia determinants on T cells was evaluated by the rosette method with Staphylococcal protein A-(SPA) coated bovine red blood cells (BRBC) or the indirect immunofluorescence method with monoclonal anti-Tac and anti-Ia antibodies. An increase in Tac-positive or Ia-positive T cells was more evident with the use of the rosette method with SPA-coated BRBC than with conventional immunofluorescence. The percentage of Ia-positive T cells showed a peak between 24 and 48 hr after toxoid injection, and remained at high levels until 2 wk after immunization. In contrast to Ia-positive T cells, the appearance of Tac-positive T cells was transient and at a rather early period of toxoid immunization. The maximum increase of Tac-positive T cells was apparent around 12 hr after toxoid injection, and Tac-positive T cells disappeared abruptly from circulation by 24 hr after inoculation. Ia-positive T cells were induced in both Leu-2 suppressor/cytotoxic and Leu-3 helper/inducer subsets, whereas Tac-positive T cells were generated only within the Leu-3 subset. The fact that induction of Tac-positive and Ia-positive T cells might occur at different stages of T cell activation and in different subsets of T cells seemed to be important for elucidating their roles in the in vivo T cell proliferation and differentiation.

Functional significance of Tac antigen expressed on activated human T lymphocytes: Tac antigen interacts with T cell growth factor in cellular proliferation.

Cultured human T cells (CTC), which are grown in conditioned medium containing T cell growth factor (TCGF), proliferate in response to TCGF. It has been shown that an antigen (Tac) defined by a monoclonal antibody, termed anti-Tac antibody, is expressed on human T cells activated by mitogens or antigens and CTC grown in the presence of TCGF. To elucidate the functional significance of Tac antigen expressed on activated T cells, we studied the effect of anti-Tac antibody on TCGF-dependent proliferation of CTC. The addition of anti-Tac antibody strongly inhibited the proliferation of CTC induced by TCGF. This inhibition was observed only when the antibody was added at the early phase of culture, but not when the addition of the antibody was delayed beyond 24 hr of culture. Seven-day-old PHA-induced T cell blasts, but not fresh peripheral blood lymphocytes, were able to absorb TCGF activity in conditioned medium, as assessed by the DNA synthesis of CTC. When PHA-induced blasts were treated with anti-Tac antibody before absorption, their capacity to absorb TCGF activity was almost completely eliminated. In contrast, absorption of TCGF by PHA-induced blasts was not significantly reduced even when they were pretreated with other monoclonal antibodies (anti-Ia, OKT9, or OKT10) with specificity for antigens expressed on activated T cells. Based on the view that TCGF interacts with activated T cells via specific membrane receptors, these observations suggested that anti-Tac antibody might specifically block the binding of TCGF to the corresponding membrane binding sites, resulting in the inhibition of TCGF-dependent proliferation of CTC. Tac antigen expressed on activated T cells seems to participate in responding process of activated T cells to TCGF.

A syndrome of periodic adrenocorticotropin and vasopressin discharge.

An 8-yr-old girl is presented who had periodic attacks of vomiting, psychotic depression, drowsiness, and hypertension (160/110 mm Hg) for a period of 16 months after head injury. At the initiation of the attack, serum ACTH and vasopressin levels were prominently increased (610 pg/ml and 41 microunits/ml, respectively), followed by hypercortisolemia, hyponatremia, and hypoosmolality in plasma. Serum PRL also was elevated (91 ng/ml). Responses of GH and cortisol to insulin-induced hypoglycemia and those of TSH to TRH were reduced. Urinary excretion of epinephrine and norepinephrine were increased, while dopamine (DA) excretion was reciprocally decreased, resulting in a marked elevation of the epinephrine plus norepinephrine to DA ratio during the episodes (0.4-4.5); this was normalized on attack-free days (0.08-0.25). During the attack, the concentration of homovanillic acid, a major metabolite of DA in the brain, also was reduced in cerebrospinal fluids from 70 to 23 ng/ml. The administration of methyl-dopa and reserpine effectively suppressed the recurrence of the episode. Although the exact cause of this syndrome is unknown, a periodic metabolic dysfunction of catecholamine in the central nervous system might be postulated.