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*
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and Departments of
Medicine and
Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98145
Memory T cells that home to inflamed tissues typically
express the ß-chemokine receptor CCR5 and exhibit a Th1 cytokine
profile. The migration of these cells into the genital tract following
antigenic exposure has particular relevance to acquisition of HIV-1
infection, because CCR5 functions as the coreceptor for most sexually
transmitted HIV-1 strains. We recently established methodology to
purify and culture mononuclear cells from the female reproductive
tract, and here we analyzed the phenotype, CCR5 expression, and
cytokine production of cervicovaginal T cells in up to 16 donors. The
proportion of mucosal T cells expressing CCR5 was markedly expanded as
compared with peripheral blood (mean 88% vs 24% in 13 donors), but
the receptor density on individual CCR5+ T cells was only
slightly increased (mean 5837 vs 4191 MEPE (molecules of equivalent PE)
units in 6 of 7 donors). Intracellular costaining for IL-2, IFN-
,
IL-4, and IL-5 revealed a Th1-type pattern in cervical T cells, with
significantly higher percentages of IL-2- and IFN--producing T cells
in the mucosa than in blood (mean 67% vs 29%). Coexpression of
surface CCR5 with intracellular IL-2 and IFN- was observed only
among T cells in the mucosa, but not among those in circulation. Thus,
we postulate that T cell homing to the genital mucosa leads to
differentiation into the combined CCR5+ Th1 phenotype.
Moreover, the predominance of CCR5+ Th1-type T cells in
normal cervical mucosa provides targets accessible for the efficient
transmission of macrophage-tropic HIV-1 variants in women following
sexual exposure.
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