The Predominant CD4 Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma.

infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of -specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4 T cells, in protective immunity to chlamydia. To determine the frequency and magnitude of Th1 cytokine responses elicited to infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with elementary bodies, Pgp3, and major outer membrane protein and measured IFN-γ-, tumor necrosis factor alpha (TNF-α)-, and interleukin-2 (IL-2)-producing CD4 and CD8 T-cell responses using intracellular cytokine staining. The majority of chlamydia-infected women elicited CD4 TNF-α responses, with frequency and magnitude varying significantly depending on the antigen used. CD4 IFN-γ and IL-2 responses occurred infrequently, as did production of any of the three cytokines by CD8 T cells. About one-third of TNF-α-producing CD4 T cells coproduced IFN-γ or IL-2. In summary, the predominant Th1 cytokine response elicited to infection in women was a CD4 TNF-α response, not CD4 IFN-γ, and a subset of the CD4 TNF-α-positive cells produced a second Th1 cytokine.