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Infection and Immunity, June 2007, p. 3021-3026, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01973-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

CD4+ Lymphocytes and Gamma Interferon Predominate in Local Immune Responses in Early Experimental Syphilis{triangledown}

Brandon T. Leader,1 Charmie Godornes,2 Wesley C. VanVoorhis,1,2 and Sheila A. Lukehart1,2*

Departments of Pathobiology,1 Medicine, University of Washington, Seattle, Washington 981952

Received 15 December 2006/ Returned for modification 21 January 2007/ Accepted 21 March 2007

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.

* Corresponding author. Mailing address: Department of Medicine, Box 359779, Harborview Medical Center, 325 Ninth Avenue, Seattle, WA 98104-2499. Phone: (206) 341-5362. Fax: (206) 341-5363. E-mail: lukehart{at}u.washington.edu

{triangledown} Published ahead of print on 2 April 2007.

Editor: W. A. Petri, Jr.

Infection and Immunity, June 2007, p. 3021-3026, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01973-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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