Zeitschrift für Immunit?tsforschung: Immunobiology最新文献

Human sera enhanced spontaneous cell-mediated cytotoxicity (SCMC), while anti-IgG (Fab') 2 treatment decreased this cytotoxic activity of human lymphocytes for an in vitro growing cell line (K-562). Trypsin treatment of the effector cells considerably decreased the cytotoxic potential. However, a significant cytotoxic activity could always be found in serumfree medium.

While these findings suggest the involvement of antibodies in the SCMC, they also reflect the existence of serum-independent (sui generis) SCMC activity of lymphocytes.

Removal of SCMC of Fc receptor bearing effector cells was performed by target cell adherence (rosetting). Separation of the target cell-bound lymphocytes was done by centrifugation on special Ficoll gradient. The depletion of SCMC effector cells resulted in a 62% reduction of SCMC and in a 39% reduction of ADCC. On the other hand, removal of Fc bearing effector cells showed a similar reduction in both ADCC (66%) and SCMC (78%).

Our results suggest that SCMC represents a complex activity, arising partly from the interactions of certain serum-derived or lymphocytes surface-bound antibodies and partly from a spontaneous cytotoxic function of the effector cells.

It is possible that the effector cells involved in both SCMC and ADCC derive from the same lymphocyte population and the differences are due mainly to the lower number of SCMC effector cells.

The adjuvanticity of the mistletoe preparation Iscador was investigated. The cellular response to sheep red blood cells (SRBC) was augmented after intracutaneous immunization with antigen and different doses of Iscador. Iscador did not change the cellular response to 2 X 10⁷ intraperitoneally administered SRBC. The IgM plaque forming cell response was accelerated and followed by an augmentation of the IgG and IgA plaque forming cell response.

Evidence is presented that the immunogenic and inflammatory capacities of Iscador contribute to its adjuvant activity. Both micro-organisms and soluble, filter-adherent constituents in Iscador possess adjuvant activity. The relation between the immunostimulating properties of Iscador and its anti-tumour activity is discussed.

The high proportion of alloreactive T lymphocytes and many of the available data on T cell receptors can be explained by one single hypothesis with four basic assumptions: A) The functional induction of T lineage cells in the thymus inherently causes a selection for V-regions that bind to major histocompatibility antigens (MHA). The type of MHA determines the functional pathway of the T cell. B) This process selects with the highest probability for binding sites with high affinity for the self-MHA, yet binding sites with high affinity for nonself-MHA and low affinity for self-MHA will also be selected with a low but finite probability. C) This positive selection for self-MHA binding V-regions is followed by a rigorous selection against self-reactive T cells during the subsequent thymic or post-thymic phase of tolerance induction. D) Most crucial for the hypothesis is, finally, the assumption that the second (negative) selection operates with a higher affinity threshold than the first (positive) selection. The negative selection thus spares T cell clones with low affinity for self-antigens. This provides a strong selective advantage for two major groups of cells, namely alloreactive cells most of which recognize nonself-MHA in complex with nonpolymorphic non-MHA determinants, cells that recognize nonself-determinants in complex with self-MHA with different degrees of restriction. One of the predictions of this hypothesis is that the proportion of alloreactive cells is relatively small among the T lineage cells that leave the thymus but increases largely during the post-thymic development of the peripheral T cell pool.

The hypothesis is not biased in respect to the underlying germ line repertoire of V genes, is in fact compatible with the simple assumption that T and B cells use the same sets of V genes.

The producer cells of interferon were studied in human leucocyte cultures stimulated by a variety of stimulants, including phytohemagglutinin (PHA), pokeweed mitogen (PWM), Corynebacterium parvum (CP) and Herpes Simplex Virus (HSV). When the cells were fractionated by the use of neuraminidase-treated sheep red blood cells (SRBC), the T cell population responded with interferon production to PHA and PWM but not to CP or HSV. However, the non-T population showed a vigorous response to the latter two stimuli. In contrast, nylon column eluate cells enriched for T cells responded well to CP and HSV with production of interferon. To resolve these contradictory data, we have used combinations of techniques. Nylon column eluate cells were further separated by SRBC and it was found that the nylon non-adherent rosetting cell did not produce interferon in response to HSV or CP whereas the nylon-nonadherent non-rosetting cell did. In additional experiments more elaborate techniques were used. Leucocytes were treated by plastic adherence and iron filings, passed over a nylon column and subsequently over an Ig-anti-Ig column, then rosetted with SRBC. Again only the non-rosetting population produced interferon. In parallel experiments the capacity of the different cell populations to lyse three types of target cells in a chromium release assay as a test for natural killer (NK) cell activity was investigated. There was some correlation between interferon production and NK cell activity. Thus, our data indicate that interferon is produced by non-T, non-B cells, possibly by cells related to NK cells.

A glycoprotein was isolated from human plasma which partially inhibited C3 carrying erythrocytes from binding to complement receptor cells (CR⁺C). Based on its physicochemical characteristics and its antigenicity this glycoprotein was identified as aI-antitrypsin (α₁-AT). The activity of α₁-AT towards-C3 and its fragments was unaffected by heating but it was destroyed by periodic acid. The isolated carbohydrate moiety of α₁-AT showed the same effect as the intact molecule. Using F(ab)₂ of IgG-anti-α₁-AT, α₁-AT could be demonstrated on Raji cells and human erythrocytes. Treatment of these CR⁺C with IgG-anti-α₁-AT resulted in a blockade of their C3 receptor activity. The results suggest, that α₁-AT interacts through its carbohydrate portion with C3 and its fragments and functions as a complement receptor molecule.