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Biomedical subjects

P M Kaye

Publications and source records attributed to P M Kaye.

49 records · Page 3Linked to original sources
PubMed1987

Antigen presentation and the response to parasitic infection.

Antigen presentation to T-cells is central to the induction and maintenance of the cell-mediated immune response. Many approaches have been used to define a complex accessory cell compartment, which performs the variety of functional roles encompassed by this term. Resulting from this, antigen presentation has become the cornerstone behind many theories of disease susceptibility and is an important consideration for vaccine design. In this article, Paul Kaye reviews aspects of antigen presentation by accessory cells with particular emphasis on how parasites and their antigens interact with this heterogeneous group of cells.

Journal Article↗
PubMed1987

Acquisition of cell-mediated immunity to Leishmania. I. Primary T-cell activation detected by IL-2 receptor expression.

In order to analyse the early stages of the T-cell response to Leishmania, bioassays for detecting low levels of IL-2 receptor expression both in bulk culture and under limiting dilution conditions have been used. Infection of C57BL/10 mice with Leishmania donovani amastigotes leads to the appearance of antigen-specific T lymphocytes bearing high-affinity IL-2 receptors 24-72 hr later. Phenotypic analysis by complement-mediated cytotoxicity indicates that these activated T cells comprise both L3T4+, Lyt2- and L3T4-, Lyt2+ populations. The data also suggest the existence of activated cells bearing both these markers. By both assay techniques, the appearance of receptor-positive populations appears transitory, with few such cells detectable at 7 days post-infection. The implications of these data for further studies of murine leishmaniasis are discussed.

Animals↗
PubMed1987

Inflammatory cells in murine visceral leishmaniasis express a dendritic cell marker.

Immunohistological studies of the murine liver following Leishmania donovani infection have been performed. We describe here the identification of cells expressing a recently defined dendritic cell marker, as detected by monoclonal antibody NLDC 145. Such cells are numerous in the developing inflammatory foci but are not detected individually at any other site in the infected liver. This finding suggests that mature tissue DC are not recruited during infection and that expression of this antigen is under precise microenvironmental control.

Animals↗
PubMed1986

Regulation of macrophage accessory cell activity by mycobacteria. II. In vitro inhibition of Ia expression by Mycobacterium microti.

In our preceding study, we showed that infection of mice with Mycobacterium microti leads to a dramatic increase in Ia expression on local inflammatory macrophage populations. However, the majority of these cells did not contain intracellular organisms. To evaluate the effect of parasitism of macrophages by M. microti, Ia-induction experiments were performed in vitro. We show here that Ia expression is increased on peritoneal macrophages treated with either crude lymphokine preparations or recombinant gamma-interferon (gamma-IFN) and that this expression is suppressed by M. microti in a dose dependent fashion. The degree of suppression varied between macrophage populations and could be achieved to a lesser extent with killed organisms. It was partially reversed with indomethacin but only poorly so at high infection levels. Inhibition of Ia expression may be of importance in the generation and maintenance of chronic infection.

Animals↗
PubMed1986

Regulation of macrophage accessory cell activity by mycobacteria. I. Ia expression in normal and irradiated mice infected with Mycobacterium microti.

CBA/Ca mice were infected by either the intravenous or intraperitoneal route with Mycobacterium microti and the subsequent changes in local macrophage populations examined. Following infection, the number of macrophages increased and they showed greater expression of both MHC Class II molecules. This response was not dependent on viability of the mycobacteria, in contrast to reports with other microorganisms such as Listeria. Studies in sublethally irradiated mice indicated that persistent antigen could give rise to a response after a period of host recovery which was radiation dose dependent. This procedure also highlighted differences in the regulation of different murine class II antigens in vivo, as seen by delayed re-expression of I-E antigens. Macrophage accessory cell function, as assessed by an in vitro T cell proliferation assay, correlated with Ia expression after fixation, but not after indomethacin treatment; this highlights the diverse nature of regulatory molecules produced by these cells.

Animals↗
PubMed1985

Immunoregulatory pathways in murine leishmaniasis: different regulatory control during Leishmania mexicana mexicana and Leishmania major infections.

The effect of whole body sublethal gamma irradiation on the subsequent growth of Leishmania mexicana mexicana and Leishmania major was studied in CBA/Ca and BALB/c mice. Whereas BALB/c mice are highly susceptible to both parasites developing non healing progressively growing lesions at the site of cutaneous infection, CBA/Ca mice develop small healing cutaneous ulcers following subcutaneous infection with L. major but non healing lesions following subcutaneous infection with L.m. mexicana. Prior whole body sublethal irradiation of CBA/Ca mice, but not BALB/c mice, resulted in strong resistance against infection with L.m. mexicana: no lesions developed at the site of cutaneous infection. Irradiated BALB/c mice did, however, develop small lesions which healed when infected with L. major. The protective effects of irradiation coincided with the development of delayed type hypersensitivity. Both naive and sensitized nylon wool purified lymphocytes could restore susceptibility to L. major in irradiated BALB/c mice but only lymphocytes from long term infected donor mice adoptively transferred a non healing response to irradiated CBA/Ca mice infected with L.m. mexicana. Non-irradiated, L. major infected, CBA/Ca mice, but not similarly treated BALB/c mice, were found to be resistant to subsequent infection with L.m. mexicana. On the other hand, irradiated BALB/c mice infected with L. major were resistant to subsequent infectious challenge with L.m. mexicana. We suggest that the susceptibility of CBA/Ca mice to L.m. mexicana is under the control of an as yet unidentified gene which is not dependent on the generation of T suppressor cells and is bypassed by previous infection with L. major. Therefore, BALB/c mice immunized against L. major by prior sublethal irradiation are also resistant to L.m. mexicana.

Animals↗
PubMed1985

Nonphagocytic dendritic cells are effective accessory cells for anti-mycobacterial responses in vitro.

The accessory cell requirements for a given T cell response may be examined in vitro by using highly purified lymph node T cells. We have examined the capacity of different antigen-presenting cells to stimulate proliferation of Mycobacterium tuberculosis-primed T cells when the antigenic challenge is either soluble or particulate in nature. By titrations of cell number and antigen concentration, it was shown that dendritic cells are not only extremely efficient at presenting soluble mycobacterial antigen compared with various macrophage populations, but also that they are capable of presenting whole mycobacteria. Because phagocytosis of mycobacteria does not occur with these cells, we suggest that processing of antigen by dendritic cells may be initiated at the plasma membrane. Because macrophages are not essential for this in vitro response, a role for dendritic cells in antibacterial immunity in vivo is implicated.

Animals↗
PubMed1983

The effect of parasitization by Leishmania mexicana mexicana on macrophage function in vitro.

Macrophages infected with amastigotes of Leishmania mexicana mexicana as compared to normal macrophages show decreased migration both randomly and through a 5 microns pore in response to a known chemotaxin, an increased ability to pinocytose and an increased bactericidal ability. Unless very heavily parasitized their ability to phagocytose is unaltered. Parasitized macrophages are unaltered in their ability to secrete extracellularly lysosomal enzymes, prostaglandins and lysozyme in response to known stimuli, or to kill target cells in an antibody dependent cell mediated cytotoxicity assay.

Animals↗
PubMedDate not supplied

Interleukin-13 in Iranian patients with visceral leishmaniasis: relationship to other Th2 and Th1 cytokines.

The role of interleukin (IL)-13, a Th2 cytokine sharing many of the features of IL-4, has not previously been examined in patients with visceral leishmaniasis (VL). We examined sera from Iranian patients with VL caused by Leishmania infantum. Serum IL-13 was detected in 50% (22/44) of patients with active primary disease. In comparison, IL-10 was detected in 79.5% (35/44), interferon gamma (IFN gamma) in 38.5% (17/44), and IL-4 in only 5% (2/44) of these patients. With few exceptions all 3 cytokines were undetectable after clinical recovery following antimony therapy. Five of 7 patients (71%) who failed antimony therapy and had relapsing disease had similar levels of IL-10 to patients with active primary disease. However, with only 1 exception, IL-13, IFN gamma and IL-4 were not detected in such patients. These data suggest that relapsing disease may result from defective cellular immunity, unrelated to immunosuppression mediated by IL-10.

Animals↗