Publications

Depletion of critical T cell subsets in vivo by treatment with anti-L3T4 antibody (mAb GK1.5) enables BALB/c mice to heal subsequent Leishmania major infection. To investigate the mechanisms by which healing is established, anti-leishmania cellular and humoral responses in anti-L3T4-treated BALB/c mice were compared to those in control BALB/c and genetically resistant C57BL/6 mice. Lymph node and spleen cells were harvested from L. major-infected animals at 1, 2, 3, 4, and 8 wk post-infection and examined in vitro for concanavalin A- or L. major antigen (either promastigote or amastigote)-induced IFN-gamma production. Serum was harvested for Western blot analysis against L. major promastigote antigens. Lymph node cells from resistant C57BL/6 mice generated Leishmania antigen-induced IFN-gamma that was maximal by 3 wk; spleen cell IFN-gamma production peaked a week later. Lymph node and spleen cells from susceptible BALB/c mice generated minimal levels of IFN-gamma activity in response to Leishmania antigen stimulation throughout the experiment. Lymph node and spleen cells from BALB/c mice which had been pretreated with GK1.5 generated IFN-gamma in response to Leishmania antigens in vitro at levels that approached those generated by C57BL/6 mice. When splenic mRNA from infected animals was hybridized with a labeled murine IFN-gamma cDNA probe, there were corresponding differences in the amount of IFN-gamma message present, demonstrating that the differences observed in IFN-gamma production in vitro were also apparent in vivo, and were due to differences in transcription. In contrast to C57BL/6 mice which generated only a limited array of Leishmania-specific antibodies, BALB/c mice produced antibodies which reacted with a large number of Leishmania antigens. The GK1.5-treated BALB/c mice developed Leishmania-specific antibodies at a slower rate than did untreated BALB/c mice. However, by 8 wk after infection, the humoral responses of the anti-L3T4-treated BALB/c mice and the untreated BALB/c mice were comparable. These data document the kinetics of ascending immunity from the draining local lymph nodes to the spleen and confirm, both in vitro and in vivo, the correlation of IFN-gamma production with control of infection in leishmaniasis. Further, an L3T4+ T cell subpopulation may be incriminated in the failure of genetically susceptible BALB/c mice to activate curative cell-mediated immunity in response to Leishmania antigens.

Ninety-seven female sexual partners of 93 men infected with human immunodeficiency virus were studied. All of the women had sexual contact within the year before their partner had been diagnosed as having acquired immunodeficiency syndrome or was found to have a positive reaction on the human immunodeficiency virus serologic test. Fifty-seven percent were the partners of bisexual men. Overall, 23% of the women were infected (95% confidence interval, 15% to 32%). The total number of exposures to the index case (sexual contacts with ejaculation) and the specific practice of anal intercourse, also with the infected partner, were associated with transmission. Neither condom use, total number of sexual partners since 1978, nor lifetime number of sexually transmitted diseases was associated with infection.

Allergic reactions to the beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, and monobactams) are a major factor limiting their use. Immediate hypersensitivity reactions to penicillins depend on the presence of preformed allergic (IgE) antibodies to several penicillin determinants. These materials can be used in in-vivo skin testing to exclude those patients at risk for immediate or accelerated allergic reactions. The cephalosporins have not had their relevant determinants defined as related to allergic reactions. The results of in-vivo challenges of patients with IgE to penicillin suggest the incidence of reactivity of cephalosporins in patients allergic to penicillin is less than generally appreciated. The monocyclic beta-lactam antibiotic, aztreonam (a monobactam), failed to show cross-reactivity with penicillin antibodies, because immune reactivity toward the monobactam was directed against side chain rather than nuclear determinants. On the other hand, the new bicyclic carbapenem beta-lactam drugs, represented by imipenem, showed extensive in-vivo cross-reactivity with penicillins.