Biomedical subjects

D E Weinstein

Publications and source records attributed to D E Weinstein.

21 records · Page 2Linked to original sources

PubMed1987

Mycobacterium leprae antigen-induced suppression of T cell proliferation in vitro.

The extent to which M. leprae and its products induced suppression of T lymphocyte proliferation in vitro was evaluated. M. leprae antigens suppressed T cell proliferation in response to mitogens and antigens in both lepromatous and tuberculoid patients, as well as controls never exposed to M. leprae or M. leprae endemic areas. Both soluble and particulate fractions of M. leprae were found to suppress proliferation in a dose-dependent manner. The extent of suppression was inversely related to the proliferative response of the donors mononuclear cells to M. leprae. Evidence indicates that M. leprae contains both stimulatory and suppressive molecules for T cells. One such suppressive antigen, Lipoarabinomannan (LAM)-B of M. leprae, also suppressed the proliferative response of tuberculoid patients. Suppression was also observed with the LAM-B of M. tuberculosis. The suppressive effects observed were not due to the toxicity of the antigen. Some of the suppressive activity was mediated by T8+ suppressor cells and was expressed in both lepromatous and tuberculoid patients. We suggest that previous sensitization to M. leprae and other cross-reactive mycobacterial antigens determines the sensitivity of T cells to the suppressive effects of M. leprae antigens.

Antigens, Bacterial↗

PubMed1985

An analysis of in vitro T cell responsiveness in lepromatous leprosy.

In lepromatous leprosy, there is extensive replication of Mycobacterium leprae (M. leprae) within dermal macrophages. This lack of microbial resistance has been attributed to a defective cell-mediated immune response to M. leprae antigens. We have examined the in vitro response of T cells to M. leprae to determine if hyporesponsiveness could be reversed. The study included 40 unselected patients from New York and from Colombia, most with the severe lepromatous form of the disease. We first noted that lepromatous leprosy patients were of two types: those unable to respond, as assessed by T cell proliferation and immune (gamma) interferon (IFN-gamma) release, and a second group, exhibiting low but detectable responses relative to tuberculoid controls. When the effect of exogenous recombinant interleukin-2 (IL-2) on the response to M. leprae antigens was compared in the two groups, many of the low responders, but not the nonresponders, showed enhanced proliferation and IFN-gamma release. To evaluate a possible suppressive effect of monocytes, these cells were eliminated with a cell-specific monoclonal antibody and complement. Depletion of monocytes often expanded preexisting weak responses but did not reverse the anergy of the M. leprae nonresponders. The enhancement was not M. leprae-specific, since it was also observed when bacillus Calmette-Guerin was the antigenic stimulus for proliferation and IFN-gamma production. Removal of the suppressor T cell subset, with OKT8 antibody and complement, also did not restore responses in nonresponder patients. We conclude that a sizable number of lepromatous leprosy patients exhibit a low degree of responsiveness to M. leprae and that the responses can be enhanced in vitro with IL-2 or with monocyte depletion. Nonresponsiveness, however, cannot be reversed. Since currently available assays measure the function of previously sensitized T cells, suppressor mechanisms may yet contribute to defective cell-mediated immunity by impairing the initial sensitization to M. leprae antigens.

Adult↗

PubMed1983

Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation.

T cells oxidized with sodium periodate proliferate polyclonally in response to accessory cells. We confirmed previous work showing that DC are potent stimulators of this response. In addition, the accessory function of unfractionated mouse spleen and spleen adherent cells was markedly reduced after elimination of DC with a specific monoclonal antibody and complement. Therefore oxidative mitogenesis was used as a model to study the mechanism by which DC stimulate T cell proliferative responses. A two-stage mechanism was identified. The first stage occurred during the first 20 h of culture, required live DC, and involved the progressive release of interleukin 2 (IL-2) into the medium and acquisition of responsiveness to this growth factor. The second stage occurred between 20 and 40 h, did not require live DC, and involved DNA synthesis in response to IL-2. Similar events occurred during culture of DC with unmodified T cells (syngeneic MLR) but were quantitatively reduced. The experimental approach was to co-culture DC and T cells for up to 20 h and then kill the DC with specific antibody, or anti-Ia antibody, and complement. Subsequent proliferation was inhibited if the T cells were cultured in fresh medium. However, proliferation was restored when the lymphocytes were cultured in the original DC-T cell medium, or with a crude or a purified preparation of IL-2. IL-2 did not induce the proliferation of T cells that had been cultured in the absence of DC, and did not synergize with viable DC. We conclude that DC induce proliferation by tightly coordinating the release of, and responsiveness to, T cell growth factor or IL-2.

Animals↗