Interleukin-2, but not interleukin-15, is required to terminate experimentally induced clonal T-cell anergy.

It has been demonstrated that T cells stimulated with nucleosome-polyomavirus T-antigen (self-nonself) complexes, but not nucleosomes, activate autoimmune nucleosome-specific T cells. As these cells may be naïve, such observations do not show that anergic T cells are reactivated. To understand the regulation of autoimmunity, this is important to assess, and this is the focus of this study. T-cell anergy was induced by antigen stimulation in the presence of antibodies to the costimulatory molecules CD80/CD86. Requirements for the reactivation of anergic T cells were analysed by the ability of antigen and interleukin-2 (IL-2) or IL-15 to increase T-cell proliferation and IL-2 transcription. Data demonstrate that stimulation of T cells with T-antigen and anti-CD80/86 antibodies promotes long-lasting clonal T-cell anergy. While T-antigen did not reactivate anergic T cells, proliferation and upregulation of IL-2 gene transcription was initiated by stimulation with antigen, costimulation and IL-2 added to the cultures. Proliferation per se was not sufficient to promote the reactivation of anergic T cells, as both IL-2 and IL-15 induced proliferation, while antigen and IL-2, but not IL-15, upregulated IL-2 mRNA levels. These data demonstrate that the innate immune system and IL-2 are central to the initiation and termination of T-cell anergy.

A longitudinal study of human cytomegalovirus serology and viruria fails to detect active viral infection in 20 systemic lupus erythematosus patients.

In this study, we investigated whether active human cytomegalovirus infection could be detected in 20 systemic lupus erythematosus (SLE) patients over a one-year observation period by polymerase chain reaction on serial urine specimens and by monitoring of IgG and IgM HCMV-specific antibody profiles in serial serum samples. Of 788 urine samples analysed for the presence of human cytomegalovirus DNA, only 2 specimens (0.25%) collected from two different patients contained genuine human cytomegalovirus sequences as determined by polymerase chain reaction and subsequent sequencing of the PCR products. These two patients had one positive sample out of 36 samples or 40 samples, respectively. Nineteen of the patients (95%) possessed IgG antibodies against human cytomegalovirus, while 9 (45%) produced IgM antibodies. However, none of the patients showed signs of an active virus infection as judged by the stable anti-HCMV IgG or IgM antibody levels during the observation period, nor was any correlation between disease activity and HCMV serology/viruria observed. Of single serum samples of 26 age- and sex-matched blood donors, 21 (81%) were HCMV IgG positive and 1 (3.8%) was IgM seropositive. In conclusion, our data fail to establish an active human cytomegalovirus infection in SLE patients.

T cell lines specific for polyomavirus T-antigen recognize T-antigen complexed with nucleosomes: a molecular basis for anti-DNA antibody production.

We have previously demonstrated that in vivo expression of the polyomavirus DNA-binding T-antigen initiated production of IgG antibodies to T-antigen and to DNA, but not to a panel of autoantigens not related to nucleosomes, indicating an antigen-selective T cell-dependent B cell response. In this study, we demonstrate that CD4-positive T cells from both normal and systemic lupus erythematosus (SLE) patients readily proliferate in response to pure T-antigen, and also to T-antigen in complex with nucleosomes. T-antigen-specific T cell lines from both normal individuals and SLE patients proliferate in response to nucleosome-T-antigen complexes, but not to nucleosomes or histones. B cells co-cultured with T-antigen-specific T cells and stimulated with nucleosome-T-antigen complexes produce anti-T-antigen and anti-DNA antibodies, indicating that such CD4-positive T cells have the potential to interact with B cells specific for individual components of nucleosome-T-antigen complexes. Thus, a non-self DNA-binding protein like polyomavirus T-antigen may initiate and maintain an antibody response to DNA when T-antigen is actively expressed.