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Regulatory (FOXP3 + ) T cells (T regs ) comprise a subpopulation of CD4I ntense research has shown that regulatory T cells (T regs ) play a fundamental role in providing peripheral tolerance against auto and foreign antigens, whereas impairment of T reg function seems to be associated with different autoimmune diseases like systemic lupus erythematodes,(1) type 1 diabetes, (2) rheumatoid arthritis (3,4) and multiple sclerosis.(5) Particularly stimulating for oncologic research was that increased frequencies of T regs with suppressive activity were found in malignant tumors and in the blood of cancer patients.(6-9) Blocking of T reg function in murine tumor models resulted in strong cellular antitumor immunity and even complete tumor destruction, (10)(11)(12)(13)(14)(15) indicating a crucial role for T regs in tumor immunity.T regs represent a subpopulation of CD4 + T cells and account for approximately 10-15% of all CD4 + T cells. The most specific marker for T regs currently available is the transcription regulator FOXP3. + T regs an evolutionary conserved region within the foxp3 locus upstream of exon-1 displays complete DNA demethylation, known as the T reg -specific demethylated region (TSDR), whereas T cells with transient FOXP3 expression and thus non-permanent suppressive function, such as transforming growth factor-β induced T regs and recently activated conventional human T cells show a fully methylated TSDR. (18)(19)(20)(21) Little is known about factors that mediate homing of T regs in different organs or tumor tissue, but experimental data suggest that an interaction between organ-specific factors and T regs is required for their expansion and homing. (22)(23)(24) A highly selective switch for specific inactivation of murine T regs was identified by Shimon Sakaguchi and his colleagues.(25) He developed an agonistic antibody that binds to murine glucocorticoidinduced tumor necrosis factor receptor family-related protein (GITR). Activation of GITR in concert with antigen-specific stimulation of T regs abrogates their suppressive activity. Applying the anti-GITR antibody to BALB/c mice 8 days after inoculation of 2 × 10 5 Meth-A fibrosarcoma cells induced a strong antitumor immune response followed by complete tumor eradication in all treated animals.(25) One concern regarding possible side-effects of GITR activation was the unintended induction of autoimmune reactions, but organ function in mice remained unaltered during therapy and no autoimmune reactions were detected. (25) Despite their viral origin and well-defined target genes, clinical trials for immune therapy of cervical intraepithelial neoplasia (CIN) lesions and cervical cancer have been mostly ineffective. (26)(27)(28)(29)(30)(31)(32)(33)(34)(35) Potentially acting as a tumor-protective shield, T reg may constitute an important reason for these failures, as their accumulation at the tumor site might render intended immunostimulation ineffective.In order to elucidate the prevalence of FOXP3 + T cells in CIN lesions, cervical cancer, colon can...