Stimulation of peripheral blood T cells by an activated T-cell line: a novel human autologous T-T lymphocyte reaction.

T lymphocyte interactions have generally been described between discrete functional subsets. In our investigation of murine T-cell interactions we described a type of T-T interaction termed the 'Syngeneic T-T Lymphocyte Reaction' in which activated T-cell clones stimulated the proliferation of resting T cells mainly through a mechanism involving cell to cell contact. To investigate whether similar reactions occur in the human immune system we used the human autoreactive T-cell line C.1 to stimulate peripheral T cells. Line C.1 cells, which are not transformed and do not secrete IL2, consistently caused proliferation of purified freshly isolated autologous peripheral human T cells as measured by a [3H]-thymidine incorporation assay. The proliferation was seen in both the CD4 and CD8 subsets and could be inhibited with anti-DR and anti-CD2 antibodies. The stimulation is not due to carryover of classical antigen-presenting cells or to the C.1 line cells acting as antigen-presenting cells. We propose that some activated T cells, probably by expression of a surface molecule, can stimulate resting T cells thereby allowing for antigen-non-specific augmentation of the immune response.

Antigenicity of passively acquired major histocompatibility antigens on T cells.

T cell blasts and lines passively acquire MHC molecules in vitro. To determine the role of these molecules in immunoregulatory reactions, we examined whether T cell lines grown on irradiated F1 spleen cells were able to supply allogeneic MHC antigens for the stimulation of T cell proliferation. Immunofluorescence analysis demonstrates that autoreactive T cell lines grown with irradiated F1 spleen cells acquire allogeneic class II molecules and subsequently lose the MHC molecules within 4 days of coculture with syngeneic cells. The proliferative response of (H-2k x H-2d)F1T cells stimulated by a T cell line grown on (H-2k x H-2d)F1 cells is inhibited by the addition of hybridoma-culture supernatants containing anti-IAd as well as anti-IEk antibodies. The proliferation of the F1 T cells to the T cell line grown on H-2k spleen cells is only affected by supernatants containing anti-IEk antibodies. To investigate the role of acquired class I MHC antigens, we examined their ability to serve as antigens for cytotoxic cells. Anti-H-2k cytotoxic T cells are generated when H-2b T cells are cultured with an H-2b-derived T cell line, only if the line has been grown on (H-2k x H-2b)F1 cells. An H-2b-derived T cell line exposed to (H-2k x H-2b)F1 cells can be lysed by anti-H-2k cytotoxic T cells from a primary MLR. Similarly, an H-2k anti-H-2b cytotoxic T cell clone will kill an H-2k-derived T cell clone grown on (H-2k x H-2b)F1 spleen cells. These results demonstrate that passively acquired class I molecules can stimulate the generation of cytotoxic T cells that lyse cells expressing the class I antigens and that passively acquired class I molecules expressed on T cells serve as the target for cytotoxic T cells.

The syngeneic T-T lymphocyte reaction (STTLR). I. Induction of primary T anti-T cell proliferative responses in T cell cultures stimulated with self- and antigen-reactive T cells.

The generally accepted "Gershonian" view of immunoregulation attributes T cell-mediated regulation of immune responses to the activities of discrete T cell subsets with specialized functions such as help, suppression, and contrasuppression. Several observations made in our laboratory are not compatible with this paradigm. For instance, careful quantitations of carrier-specific T cell help to hapten-specific B cells in an adoptive transfer system yielded complex dose-response curves that could not be explained on the basis of interactions between discrete subsets of helper and suppressor cells. Rather, the results were most easily interpreted according to a model based on the following assumptions: (1) Regulation of helper T cell activity is a dose-dependent, dynamic property of T cell populations that exhibit a high degree of connectivity (self-recognition) and (2) helper T cells have the ability to perform different functions, depending on the current activity of other interacting lymphocytes. A good example of cloned T cells capable of performing multiple immunoregulatory functions was provided by the IEk-specific self-reactive Lbd line which provided help, suppression, and contrasuppression to T cell dependent PFC responses (see Quintáns et al., 1986). Since these effects were strictly dependent on the levels of antigen-specific T cell help, we hypothesized that Lbd cells interacted with other T cells to modulate their function. In this paper, we directly test the hypothesis that activated T cells can interact directly with resting T cells and describe the proliferative component of a syngeneic T cell anti-T cell response induced by antigen and self-reactive helper and cytotoxic T cells. In a follow-up report, we will describe the effector component of the T anti-T cell response.(ABSTRACT TRUNCATED AT 400 WORDS)

Infection with CDC group DF-2 gram-negative rod: report of two cases.

Two patients had bacteremia with Center for Disease Control group DF-2 Gram-negative rods. Previously described patients infected with this organism had clinical syndromes including cellulitis, meningitis, and endocarditis, and generally were severely ill. One of our patients had acute oligoarticular arthritis. The other had fever, headache, malaise, and a generalized rash. In neither case was bacterial infection considered likely at onset, and neither patient received antibiotic therapy. Both patients recovered completely. The organism is a fastidious Gram-negative rod that only recently has been characterized. Methods for isolating and identifying the organism are reviewed. The spectrum and frequency of illnesses caused by this organism are probably greater than previously recognized.

Effects of digoxin-specific antibodies on accumulation and binding of digoxin by human erythrocytes.

THE PRESENT STUDIES INDICATE THAT ACCUMULATION OF DIGOXIN BY INTACT HUMAN ERYTHROCYTES IS THE RESULT OF TWO PROCESSES: binding of digoxin to the erythrocyte membrane and uptake of digoxin across the membrane into the cell. In contrast, accumulation of ouabain by human erythrocytes is entirely attributable to binding of this glycoside to the plasma membrane. Digoxin binding to the erythrocyte membrane involves a single class of binding sites, is a saturable function of the extracellular digoxin concentration, reversible, temperature-sensitive, dependent on the cation composition of the incubation medium, inhibited by other cardioactive steroids, and correlates with the inhibition of erythrocyte potassium influx. Digoxin uptake across the membrane into the cell is also temperature-sensitive and reversible but is a linear function of the extracellular digoxin concentration, not altered by changes in the cation composition of the incubation medium, not inhibited by other cardioactive steroids, and does not correlate with inhibition of erythrocyte potassium influx. Digoxinspecific antibodies can both prevent and reverse effects of digoxin on potassium influx in human erythrocytes by virtue of the capacity of the antibodies to decrease the amount of digoxin that is bound to the erythrocyte membrane. These antibodies also reduce uptake of digoxin across the plasma membrane into the erythrocyte; however, this portion of cellular digoxin is not responsible for the observed inhibition of potassium influx. In the presence of digoxin-specific antibodies, the changes in digoxin binding to the erythrocyte membrane and in digoxin uptake across the membrane into the cell reflect the ability of the antibodies to form complexes with "free" digoxin molecules in the incubation medium and thereby decrease the effective concentration of digoxin.