Objective. We previously reported that the Val58Ile polymorphism of the leukocyte cell-derived chemotaxin 2 gene (LECT2) is associated with the severity of rheumatoid arthritis (RA). To define the role of LECT2 in inflammatory arthritides, we investigated the development of collagen antibody-induced arthritis (CAIA) in LECT2-deficient (LECT2 ؊/؊ ) mice.Methods. CAIA was induced in mice by administering anti-type II collagen antibodies followed by lipopolysaccharide. Daily assessment of hind paw swelling was used to monitor the development of arthritis. The histopathologic features and expression of inflammatory cytokines were also analyzed. We confirmed the role of LECT2 by introducing a LECT2 expression vector into LECT2 ؊/؊ mice, using a hydrodynamic gene transfer method.Results. Arthritis in LECT2 ؊/؊ mice was significantly exacerbated compared with that in wild-type (WT) controls. Histopathologic assessment of the tarsal joints showed that inflammation and erosion of cartilage and bone in LECT2 ؊/؊ mice were more severe than that in controls. Interleukin-1␤ (IL-1␤), IL-6, and certain chemokines were present at significantly higher levels in the arthritic hind paws of LECT2 ؊/؊ mice. In contrast, the amount of LECT2 in the serum and locally in the hind paws was higher in arthritic WT mice. Finally, hydrodynamic gene transfer experiments revealed that the severity of arthritis was reduced by the systemic expression of exogenous mouse LECT2 protein in LECT2 ؊/؊ mice.Conclusion. These results strongly suggest that LECT2 directly suppresses the development of CAIA. Manipulation of LECT2 might provide a rationale for novel therapeutic approaches to the treatment of inflammatory arthritides such as RA.

Peripheral blood T lymphocytes of Old World monkeys, rhesus and cynomolgus monkey (Macaca mulatta and Macaca fascicularis, respectively), were successfully immortalized by infection with Herpesvirus saimiri subtype C. The T cell lines were stably cultured without addition of exogenous IL-2. The STP-C488 protein, the oncogene product of subtype C strain 488-77, was detected in these cells by Western blotting. They also expressed some markers of activated or matured T cell phenotypes such as CD2+, monkey Pan-T+, CD25+,CD29+ and MHC-II DR+. Interestingly, not only CD4+CD8- or CD4-CD8+ single positive subpopulations but also CD4+CD8+ double positive ones were present in all of them. Furthermore, they were productively infected with both SIVmac and SIVagm. The levels of the viral replication were comparable to those in human T cell lines. Thus, Herpes Virus Saimiri-immortalized Old World monkey T lymphocytes will be suitable for further studies of immune system in Old World monkeys and cell-virus interactions in SIV infection.

The quantitative and phenotypic changes of peripheral blood monocytes during the acute stage of simian immunodeficiency virus infection were investigated. We inoculated intravenously three cynomolgus monkeys (Macaca fascicularis) with 100 TCID50 of SIVmac239 and collected whole blood twice a week until 35 days postinoculation. We found that the relative number of monocytes in peripheral blood leukocytes significantly increased at 7-17 days postinoculation. This increase was concomitant with the peak of primary SIV antigenemia. To determine if the monocytes observed during the acute stage were phenotypically altered, they were periodically examined for the expression of surface markers (i.e., CD11b, CD14, CD16, CD29, D32, CD56, CD62L, CD64, CD80, and MHC-II-DR) by flow cytometry. The results showed that the expression levels of CD14 and CD56 on most of the monocytes were remarkably reduced at 7-17 days postinoculation, and a new subpopulation, CD14lowCD16+CD80+ monocytes, was clearly detected at 10 days postinoculation. These results indicate that the phenotypic alteration of peripheral blood monocytes occurs during the primary SIV infection.

The pathogenesis of AIDS virus infection in a nonhuman primate AIDS model was studied by comparing plasma viral loads, CD4؉ T-cell subpopulations in peripheral blood mononuclear cells, and simian immunodeficiency virus (SIV) infection in lymph nodes for rhesus macaques infected with a pathogenic molecularly cloned SIVmac239 strain and those infected with its nef deletion mutant (⌬nef). In agreement with many reports, whereas SIVmac239 infection induced AIDS and depletion of memory CD4