T helper type-1 (Th1)/Th2 profiles of peripheral blood mononuclear cells (PBMC); responses to antigens of Chlamydia trachomatis in subjects with severe trachomatous scarring

Abstract

SUMMARYIncreased stimulation of Th2 cytokines may contribute to the development of persistent ocular chlamydial infection, resulting in the blinding pathological changes of trachoma. Proliferation and cytokine production profiles of PBMC in response to stimulation with antigens of Chlamydia trachomatis were compared in 30 patients with severe conjunctival scarring due to trachoma and in 30 age-, sex-and location-matched controls. Interferon-gamma (IFN-°) and IL-4 were detected at the single-cell level by ELISPOT assay. Transcription of the genes encoding IFN-°, IL-4 and IL-10 was detected in mRNA isolated from parallel cultures of PBMC using reverse transcriptase-polymerase chain reaction (RT-PCR). Incubation with the chlamydial heat shock protein (hsp)60 resulted in increased numbers of IL-4-producing cells in PBMC isolated from patients with scarring disease and increased secretion of IFN-°from PBMC of control subjects. Incubation with the chlamydial major outer membrane protein (MOMP) increased the number of IFN-°-producing cells in the control group only. Messenger RNA encoding IL-4 was only detected in PBMC of patients with scarring disease after in vitro stimulation with chlamydial antigens, but IFN-°mRNA and IL-10 mRNA were also more frequently detected in this group. Thirty-eight subjects were HLA-DRB1 and -DQB1 typed. Associations were observed between certain HLA class II alleles and cellular immune responses to chlamydial antigens. No HLA associations were found with clinical status, and overall we found no evidence of strong associations and the type of immune response. These data are consistent with a role for Th2 cells and cytokines in the pathogenesis of trachomatous scarring.

Crucial role of interleukin‐10/interleukin‐12 balance in the regulation of the type 2 T helper cytokine response in reactive arthritis

“…Therefore, our results suggest that failure to mount an effective Thl response to eliminate ReAtriggering bacteria might be a relevant pathogenetic factor in ReA, as has also been suggested for severe trachomatous scarring after infection of the eye with C trachomatis (50). The presence of HLA-B27 might be more relevant for chronic courses and for the development of spondylarthropathy-specific features than for the pathogenesis of acute ReA (7,8,20).…”

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

“…High ex vivo IL10 production by lymphocytes from patients with scarring trachoma (TS) has also been observed. 16 Evidence from a twin study suggested that genetic variation influences the host immune response to trachoma. 17 We have identified associations between trachomatous scarring and HLA class I and II alleles, and with single-nucleotide polymorphism (SNPs) at the TNFa and IL10 loci in Gambians in previous studies.…”

Adoptive Transfer of CD8α+ Dendritic Cells (DC) Isolated from Mice Infected with Chlamydia muridarum Are More Potent in Inducing Protective Immunity Than CD8α− DC

“…We previously found that the mouse strain that produces higher organism-driven IFN-␥ production shows significantly more resistance to chlamydial infection (10,17) and that IFN-␥ gene knockout (KO) mice, IL-12 KO mice, and IL-18 KO mice exhibit much more serious diseases when compared with wild-type mice (27,28). Studies by other groups also demonstrated the extreme importance of IFN-␥ and Th1 immune responses in host defense against chlamydial infection (14,22,23,25). Dendritic cells (DC) have been shown to be the most efficient APC in priming T cells.…”