CD4+ lymphocytes and gamma interferon predominate in local immune responses in early experimental syphilis.
The clearance of Treponema pallidum subsp. pallidum from early syphilis lesions involves infiltration of a large number of mononuclear cells and is characteristic of a cell-mediated immune response. In the present study, we sought to determine the relative abundance of different T-lymphocyte populations and Th1/Th2-associated cytokines present in testicular lesions following experimental infection with the Chicago strain of T. pallidum. Using flow cytometry, we examined the proportion of CD4(+) and CD8(+) T cells present throughout the progression and resolution of primary syphilis in the rabbit model. We related these findings to the results of real-time reverse transcription-PCR quantification of treponemal and cytokine mRNA levels. Treponemal mRNA levels reached peak values on day 18 postinfection, coincident with an initial peak in the level of T cells, which were primarily CD4(+) T cells. T-cell levels increased again during resolution of orchitis, and there was an increased proportion of CD8(+) T cells. The maximum gamma interferon (IFN-gamma) and interleukin-10 (IL-10) mRNA levels were observed on days 11 and 18, respectively, while only negligible amounts of IL-4 and IL-2 were detected throughout the infection. In addition to showing the temporal relationship between treponemal burden and T-cell responses during lesion progression, our results also demonstrate that the composition of the T-cell population changes during lesion resolution. The presence of the mRNA for IFN-gamma, but not IL-4, is consistent with cytokine expression in human syphilis and provides further support for the hypothesis that there is a Th1 predominance during the early immune response to T. pallidum.
Leader
Brandon T
BT
Department of Medicine, University of Washington, Harborview Medical Center, 325 Ninth Avenue, Seattle, WA 98104-2499, USA.
Godornes
Charmie
C
VanVoorhis
Wesley C
WC
Lukehart
Sheila A
SA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013587:Syphilis / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D014210:Treponema pallidum / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology
D012333:RNA, Messenger; D007371:Interferon-gamma