Interferon treatment of mice: enhanced expression of histocompatibility antigens on lymphoid cells.

Abstract

Treatment of young and mature mice with potent mouse, interferon preparations results in a marked enhancement of the expression of histocompatibility antigens on the surface of thymocytes and splenic lymphocytes as measured by an enhanced absorption of alloantiserum. We postulate that such modifications of the cell surface may reilect an effect of interferon on lymphocyte maturation and may be relevant to the effect of interferon on lymphocyte function.Since interferon can affect both the division and function of lymphocytes (1-17) it seems likely that it plays a role in the regulation of the humoral (6-11) and cell-mediated immune response (1,2,(12)(13)(14)(15)(16)(17). We have recently shown that incubation of mouse lymphoid cells with interferon was accompanied by a marked enhancement of the expression of surface histocompatibility antigens (18). The availability of potent semi-purified mouse interferon preparations (19) enabled us to determine whether treatment of mice with interferon would also result in modifications in the expression of histocompatibility antigens on thymocytes and splenic lymphocytes. (18) but may be summarized here as follows: spleen or thymus was homogenized gently in a Ten-Broek grinder with Eagle's minimal essential medium, and after sedimentation of large clumps of tissue the cell-rich supernatant was centrifuged. The cell sediment was washed once. Cell concentrations from control or interferontreated mice were adjusted so that the initial tube contained 20 X 106 splenic lymphocytes per ml or 40 X 106 thymocytes per ml. (Cell viability was determined by the trypan blue dye exclusion method. Cell mortality was always below 10%.) Tubes containing 2-fold dilutions of cells (in 1 ml) were centrifuged for 5 min at 800 X g in a refrigerated International Centrifuge. The supernatant was drained off and the cell sediment was incubated for 1 hr with an appropriate antiserum dilution corresponding to one cytotoxic unit, which is defined as % the dilution of antiserum which gave a 95% lytic end point in the cytotoxicity assay. The cells were again sedimented by centrifugation and 0.05 ml of the supernatant was harvested and assayed for remaining complement-dependent cytotoxicity for 5lCr-labeled L1210 target cells.To test the reliability (i.e., reproducibility) of this technique, a cell suspension was prepared from a pool of four spleens and several series of 2-fold dilutions were prepared from the same original cell suspension. Two such experiments comprised six series of 2-fold cell dilutions from a given cell suspension and a third experiment comprised eight series of 2-fold cell dilutions. It was found that the absorption curves (% specific 51Cr release from target cells after incubation with residual antiserum) were virtually superposable and the percent standard error at the 50% reduction point was 8%, 1%, and 15%, respectively.

A transcriptional enhancer and an interferon-responsive sequence in major histocompatibility complex class I genes.

“…In addition, there is convincing 2CAT (A) or CAT3M-L1(+) (B). Panels C and D: CAT assays evidence that the expression of class I genes can be modubssing the effects of interferon on L-cell lines L-L1(+)2 (C) and lated by exogenous factors like mitogens, immunomodula-1(+)dll (D), stably transfected with CAT3M-Ll(+) and tors, and infectious agents (19,22). Such alterations in the 173M-Ll(+)dl, respectively.…”

The Presence of -Interferon in Human Amniotic Fluid

“…It can modify the distribution and, thus, the expression of cell membrane antigens (Lindahl et al, 1976), affect the phenotypic expression of cells (Chany & Vignal, 1970), the synthesis of the cytoskeleton (Pfeffer et al, 1980;Bourgeade et al, 1981;Chany, 1981) and decrease cell multiplication (Paucker et al, 1962). Fowler et al (1980) have recently identified an interferon-like substance present in pools of murine placentas, the amount of which increased progressively during gestation.…”

Functional expression of a heterologous major histocompatibility complex class I gene in transgenic mice.

“…Part of the immune defense strategy against virally infected cells is the production of interferons (IFNs), which have the effect of increasing the level of class I antigens in a wide variety of cell types (6,9,21,27). As a consequence of this augmentation, presentation of foreign antigens to the appropriate immune effector cells may be facilitated.…”