Publications

BALB/c mice develop fatal illness following infection with Leishmania major despite expansion of helper L3T4+ T cells in the draining lymph nodes and spleen. Healer mice, either genetically resistant C57BL/6 or BALB/c that have been pretreated with monoclonal antibody GK 1.5, also develop expanded numbers of L3T4+ T cells at the time of healing. Lymph node cells from healer mice produce gamma-interferon in vitro and message for gamma-interferon can be recovered from the lymph nodes during healing in vivo. Conversely, cells harvested from non-healer mice during the course of infection produce minimal gamma-interferon in vitro and have little message for gamma-interferon detectable in vivo. When the same Northern blots are hybridized for IL-4, large amounts of IL-4 message are detected only in cells from non-healer mice. The data are consistent with the expansion of type 1 helper cells (Th1) during healing and type 2 helper cells (Th2) during progressive leishmania infection.

Tuberculosis has been reported previously in patients with acquired immunodeficiency syndrome who are at increased risk of prior infection with Mycobacterium tuberculosis. We performed a population-based study of AIDS and tuberculosis in San Francisco using the Tuberculosis and AIDS Registries of the San Francisco Department of Public Health. Of 287 cases of tuberculosis in non-Asian-born males 15 to 60 yr of age reported from 1981 through 1985, 35 (12%) also had AIDS, including 23 American-born whites. Patients with tuberculosis and AIDS were more likely to be nonwhite and heterosexual intravenous drug users than were AIDS patients without tuberculosis. Fifty-one percent had tuberculosis diagnosed before AIDS, and 37 percent had AIDS diagnosed at least 1 month prior to the diagnosis of tuberculosis. Although the lungs were the most frequent site of tuberculosis in both AIDS and non-AIDS patients, 60% of the AIDS group had at least 1 extrapulmonary site of disease compared to 28% of the non-AIDS group (p less than 0.001). Nonsignificant tuberculin skin tests were more common in AIDS patients (14 of 23 patients tested) than in non-AIDS patients (12 of 129 patients tested; p less than 0.0001). Chest radiographs in AIDS patients showed predominantly diffuse or miliary infiltrates (60%), whereas non-AIDS patients had predominantly focal infiltrates and/or cavitation (68%). Response to antituberculosis therapy was favorable in AIDS patients, although adverse drug reactions occurred more frequently than in non-AIDS patients (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

The adult T cell leukemia (ATL) is a T cell neoplasm etiologically associated with human T lymphotropic virus type I (HTLV-I) infection. ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover. Whereas interleukin 1 (IL-1) is not generally recognized as a product of T cells, this cytokine is capable of both altering IL-2 receptor expression and activating osteoclasts. Thus, we investigated the possibility that primary ATL leukemic T cells and HTLV-I-infected long-term ATL cell lines produce IL-1. S1 nuclease protection assays demonstrated that primary leukemic ATL cells from five out of six patients, as well as one patient with T4+ chronic lymphocytic leukemia, contained considerable quantities of IL-1 beta messenger RNA (mRNA) and small amounts of IL-1 alpha mRNA. These primary leukemic T cells also released biologically active IL-1 protein as evaluated in the murine thymocyte comitogenesis bioassay. In contrast to primary tumor cells, four out of six long-term ATL cell lines produced variable amounts of IL-1 alpha mRNA in the absence of detectable IL-1 beta mRNA as measured by S1 nuclease protection. These data demonstrate that IL-1 gene (especially IL-1 beta) expression occurs in many primary HTLV-I-infected leukemic T cells raising the possibility that this mediator may play a role in the pathological changes associated with this leukemia. Also, these studies show that the pattern of IL-1 alpha and IL-1 beta gene expression differs between primary ATL tumor cells and long-term cultured ATL cell lines, indicating an interesting biological difference in these two HTLV-I-infected cell populations.