The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1998/5/1633/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 10, May 18, 1998 1633-1640

Articles

Characterization of Human CD8+ T Cells Reactive with Mycobacterium tuberculosis–infected Antigen-presenting Cells

David M. Lewinsohn*,{ddagger}, Mark R. Alderson§, Andria L. Briden{ddagger}, Stanley R. Riddell||, Steven G. Reed{ddagger},§, and Kenneth H. Grabstein§

From the * Division of Pulmonary & Critical Care Medicine, University of Washington, Seattle, Washington 98104; the {ddagger} Infectious Disease Research Institute, Seattle, Washington 98104; the § Corixa Corporation, Seattle, Washington 98104; and the || Fred Hutchinson Cancer Research Center, Seattle, Washington 98104

Previous studies in murine models, including those using the β2 microglobulin knockout mouse, have suggested an important role for CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). At present, little is understood about these cells in the human immune response to tuberculosis. This report demonstrates the existence of human Mtb-reactive CD8+ T cells. These cells are present preferentially in persons infected with Mtb and produce interferon {gamma} in response to stimulation with Mtb-infected target cells. Recognition of Mtb-infected cells by these CD8+ T cells is restricted neither by the major histocompatibility complex (MHC) class I A, B, or C alleles nor by CD1, although it is inhibited by anti–MHC class I antibody. The Mtb-specific CD8+ T cells recognize an antigen which is generated in the proteasome, but which does not require transport through the Golgi-ER. The data suggest the possible use of nonpolymorphic MHC class Ib antigen presenting structures other than CD1.

Key Words: Mycobacterium tuberculosis • CD8+ lymphocytes • intracellular pathogens • antigen presentation • interferon {gamma}

Address correspondence to David M. Lewinsohn, Infectious Disease Research Institute, Box 358080, 1124 Columbia St., Seattle, Washington 98104. Phone: 206-754-5755; Fax: 206-754-5715; E-mail: dml{at}u.washington.edu

This work was presented in part at the ASM Conference "Tuberculosis: Past, Present, and Future", Copper Mountain, CO, July 8–12, 1997.

Abbreviations used: DC, monocyte-derived dendritic cells; ER, endoplasmic reticulum; FBS, fetal bovine serum; LCL, lymphoblastoid cell line; Mtb, Mycobacterium tuberculosis; PPD, purified protein derivative; SI, stimulation index.


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