Mathew Vadas

Hemopoietic colony-stimulating factors

Hemopoietic colony-stimulatingfactors (CSFs) are glycoproteingrowth factors produced by many tissues in the body; they are essential for the survival, growth and differentiation of hemopoietic progenitor cells in vitro. In this article Nicos Nicola and Mathew TTadas discuss the classes of CSF that have now been purified (M-CSF, GM-CSF, G-CSF and Multi-CSF). Each is active in vitro at picomolar concentrations, but each can be distinguished from the others by its unique molecular properties and unique spectrum of biological activity. In addition to their proliferative effects, these regulators also appear able to stimulate functional activities in mature hemopoietic cells.

Regulation by the H-2 gene complex of delayed type hypersensitivity

Identity at the major histocompatibility complex (MHC) was essential for successful transfer of delayed type hypersensitivity (DTH) in mice. The regions of the MHC involved differed according to the antigen used for sensitization. In the case of fowl gamma globulin (FGG), identity atI-A was necessary, whereas with dinitrofluorobenzene (DNFB), identity at theK, I, orD region was sufficient. These different genetic constraints probably reflect differences in the mechanisms by which antigens are presented to T lymphocytes. Cells from sensitized (CBA×C57BL)F1 mice transferred DTH to FGG into parental-strain mice, but transfer was more effective in C57BL than in CBA with the same cell dose. This phenomenon is governed by the MHC, since there was better transfer intoH-2b than intoH-2k mice, regardless of their backgrounds. It may reflect the activity of an Ir gene-dependent process. Cells of one genotype (e.g., CBA), sensitized in chimeric mice derived from two MHC-incompatible strains (CBA↔C57BL), transferred DTH to both strains. These results do not support the notion that the genetic constraint observed in DTH transfer may be a result of the necessity for sensitized T and stimulator cells to match an identical MHC-coded cell interaction molecule. Rather, they favor the hypothesis that T cells recognize antigen, not as a naked determinant, but in close association with products of genes of the MHC.

Pertussigen enhances antigen-driven interferon-γ production by sensitized lymphoid cells

Abstract We have studied the effects on interferon-γ (IFN-γ) production of pertussigen, a protein toxin from Bordetella pertussis that augments and prolongs delayed-type hypersensitivity (DTH) reactions. Lymphoid cell suspensions from immunized mice were incubated with antigen or mitogen, and the culture supernatants were assayed for IFN-γ. The production of IFN-γ on exposure to specific antigen or concanavalin A was greatly enhanced if mice were given pertussigen at the time of immunization. There was no detectable IFN-γ production when cells were exposed to saline or to an irrelevant antigen. The effect of pertussigen on antigen-driven IFN-γ production correlated with its effect on the capacity of the same cell populations to transfer DTH. The enhanced IFN-γ production by cells from mice given pertussigen could not be attributed to an increased antigen-presenting capacity of this cell population. Production of IFN-γ was abolished if the cells were pretreated with emetine, but not with mitomycin C, and the release of IFN-γ was not detected in the first 8 hr of culture. After immunization with pertussigen, IFN-γ was produced by lymph node and spleen cells from 7 days onward and both cell types produced IFN-γ until at least 30 days after immunization. It is suggested that the augmentation of antigenspecific IFN-γ production may contribute to the prolonged DTH reactions induced by pertussigen in vivo.

Evidence for the control of Eosinophilia by the major histocompatibility complex in mice

The genetic control of eosinophilia has been studied in congenic strains of mice. Eosinophilia was induced with cyclophosphamide followed by keyhole limpet hemocyanin in complete Freunds adjuvant. After this treatment, BALB/c mice developed a high eosinophil response, whereas CBA, C57BL and A/J mice developed a low one. The major histocompatibility complex (M-HQ was found to exert a control on eosinophilia, as B 10.D2 mice developed a higher eosinophil response than B10, B10.A, or B10.BR. BALB/c-H-2k mice had a lower response than BALB/c, and A.TL mice had a higher response than A/J or A.TH. If a single gene within the MHC is responsible for these effects, the most likely position for it is in the vicinity of the Tla locus. Splenectomy reduced eosinophilia in BALB/c and A.TL mice, but not in A/J mice,indicating that the spleen is a significant site of eosinophil production in high responder strains.

Parasite immunity and the major histocompatibility complex.

Parasite infestations offer fertile ground for investigation of the relationship between immunity, disease and the major histocompatibility complex (MHC). However, due to the complexities of parasite life cycles and the success of parasites in evading the immune response, immune reactions against the parasite often do not parallel protective immunity, and immunity does not imply lack of disease. — An additional level of complexity is introduced in some forms of parasite immunity by accessory effector cells, e. g., macrophages and eosinophils, that need to be ‘activated’ for maximal effectiveness, and the ‘activated’ form of these cells may partly compensate for a deficiency in specific immune responses. — It is not surprising, therefore, that polygenic effects operate in parasite immunity and reports linking non-MHC genes with parasite immunity far out number those linking MHC genes with it. From the reports that do link MHC genes with parasite immunity, two areas emerge that are interesting. First, the increased incidence of certainHLA genes in people with schistosomiasis who develop hepatosplenic disease may pinpoint individuals at risk of morbidity and direct early treatment to them. Second, mechanisms that intimately involve MHC products but are not linked to a particular MHC haplotype, may indicate newer areas in the investigation of parasite immunity.

Differences between virgin and memory IgM-antibody-forming-cell precursor B-cells, and correlations with the heterogeneity present in B-cell populations from unimmunized mice☆

Abstract Previous in vitro studies showed that a large proportion of DNP-reactive B-cells in the spleens of unimmunized mice, unlike B-cells reactive to fowl gamma globulin (FGG), did not adhere to glass-bead columns. B-cell reactivity was assessed by challenge with dinitrophenylated-polymerized flagellin (DNP-POL) or FGG in the presence of POL, both responses being thymus-independent. Now we have shown that when donor mice are immunized with FGG, a greater proportion of FGG-reactive B-cells becomes non-adherent and the column filtrates give an IgM anti-FGG response. This indicates then that the adherence properties of the IgM-producing antibody-forming-cell (AFC)-precursor differed in virgin and immunized B-cell populations. In vitro testing of the thoracic duct cell (TDC) population of normal and immunized mice revealed parallels between thoracic duct B-cells and the non-adherent splenic B-cell population. Thus while the in vitro anti-DNP response of thoracic duct lymphocytes from normal mice reached levels little below those of spleen cells, the anti-FGG response was much lower. However when TDC were taken from mice immunized with FGG, the anti-FGG responses were much higher. Thus a parallel was demonstrated both in terms of non-adherence to glass and presence in the thoracic duct, of a portion of the DNP-reactive B-cell population in un immunized mice and the FGG-reactive population in FGG-immunized mice. This suggested that the non-adherent DNP-reactive B-cells in unimmunized mice may represent B-cells with experience of cross-reacting antigens. The significance of this heterogeneity of the B-cell populations reactive to certain antigens in unimmunized mice is discussed with particular reference to recent apparently contradictory findings in regard to B-cell activation.