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 Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-10-3034.

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2002-10-3034v1
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Blood, 1 July 2003, Vol. 102, No. 1, pp. 180-183

IMMUNOBIOLOGY

Lack of the CD8+ cell anti-HIV factor in CD8+ cell granules

Carl E. Mackewicz, Baikun Wang, Sunil Metkar, Matthew Richey, Christopher J. Froelich, and Jay A. Levy

From the Rheumatology Research Laboratory, Women's Hospital, Evanston Northwestern Healthcare, IL; and the Department of Medicine and Cancer Research Institute, University of California School of Medicine, San Francisco.

In HIV infection, CD8+ cells show cytotoxic and noncytotoxic anti-HIV activity. The latter function is mediated, at least in part, by a secreted antiviral protein, the CD8+ cell antiviral factor (CAF). Because antiviral effector molecules, such as perforin and granzymes, reside in the exocytic granules of CD8+ T cells, we examined the possibility that granules contain CAF-like activity. CD8+ cells from HIV-infected individuals showing strong CAF-mediated antiviral activity were induced to release their granule constituents into culture media. Within 1 hour of stimulation, high levels of granzyme B (a primary granule constituent) were found in the culture fluids of previously activated CD8+ cells. The same culture fluids contained no or very low amounts of CAF activity, as measured with HIV-infected CD4+ cells. Maximal levels of CAF activity were not observed until 5 or 7 days after stimulation, consistent with typical CAF production kinetics. In addition, extracts of granules purified from antiviral CD8+ cells did not show any CAF activity, whereas the cytoplasmic fraction of these cells showed substantial levels of antiviral activity. These findings suggest that CAF does not reside at appreciable levels in the exocytic granules of antiviral CD8+ T cells. (Blood. 2003;102: 180-183)


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