The Journal of Experimental Medicine
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Published online 21 August 2000.
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© The Rockefeller University Press, 0022-1007/2000/8/507/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 4, August 21, 2000 507-516

Original Article

Preformed Membrane-Associated Stores of Interleukin (Il)-12 Are a Previously Unrecognized Source of Bioactive IL-12 That Is Mobilized within Minutes of Contact with an Intracellular Parasite

Marlon Quinonesa,b, Sunil K. Ahujaa,b, Peter C. Melbya,b, Lyle Pateb, Robert L. Reddickc, and Seema S. Ahujaa,b

a South Texas Veterans Health Care System, Audie L. Murphy Division, the
b Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900
c Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900
Department of Medicine (MC 7870), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900.210-567-4654210-567-4691

ahuja{at}uthscsa.edu

The prevailing paradigm is that production of the interleukin (IL)-12 p70 heterodimer, a critical T helper cell type 1 (Th1)–inducing cytokine, depends on the induced transcription of the p40 subunit. Concordant with this paradigm, we found that dendritic cells (DCs) produced IL-12 p70 only after at least 2–4 h of stimulation with lipopolysaccharide plus interferon {gamma}. However, using several complementary experimental approaches, including electron and confocal microscopy, we now show that resting murine and human myeloid cells, including macrophages/DCs and DC-rich tissues, contain a novel source of bioactive IL-12 that is preformed and membrane associated. These preformed, membrane-associated IL-12 p70 stores are released within minutes after in vitro or in vivo contact with Leishmania donovani, an intracellular pathogen. Our findings highlight a novel source of bioactive IL-12 that is readily available for the rapid initiation of Th1 host responses to pathogens such as Leishmania species.

Key Words: IL-12 p70 • dendritic cells • Th1/Th2 • Leishmania • membrane

Abbreviations used in this paper: DC, dendritic cell; EM, electron microscopy; ICAM-1, intercellular adhesion molecule 1.

© 2000 The Rockefeller University Press


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