Developmental pathways of γδ T cells are still unknown, largely because of the absence of recognized lineage-specific surface markers other than the TCR. We have shown that porcine γδ thymocytes can be divided into 12 subsets of the following two major groups: 1) CD4− γδ thymocytes that can be further subdivided according to their CD2/CD8αα phenotype, and 2) CD4+ γδ thymocytes that are always CD1+CD2+CD8αβ+ and have no counterpart in the periphery. In this study, we have analyzed γδ thymocyte subsets with respect to behavior during cultivation, cell cycle status, and lymphocyte-specific transcripts. The group of CD4− γδ thymocytes gives rise to all γδ T cells found in the periphery. Proliferating CD2+CD8−CD1+CD45RC− γδ thymocytes are a common precursor of this group. These precursors differentiate into CD2+CD8αα+, CD2+CD8−, and CD2−CD8− γδ T cell subsets, which subsequently mature by loss of CD1 and by eventual gain of CD45RC expression. In contrast, the group of CD4+ γδ thymocytes represents transient and independent subsets that are never exported from thymus as TCRγδ+ T cells. In accordance with the following findings, we propose that CD4+CD8αβ+ γδ thymocytes extinguish their TCRγδ expression and differentiate along the αβ T cell lineage program: 1) CD4+ γδ thymocytes are actively dividing; 2) CD4+ γδ thymocytes do not die, although their numbers decreased with prolonged cultivation; 3) CD4+ γδ thymocytes express transcripts for RAG-1, TdT, and TCRβ; and 4) CD4+ γδ thymocytes are able to alter their phenotype to TCRαβ+ thymocytes under appropriate culture conditions.

No abstract

The dimorphic sequence at codon 73 (73(A/A)) of the V1-69 gene contributes to genetic susceptibility in SE(-) Czech RA patients.

Background Genetic polymorphisms, such as the polymorphisms of vitamin D receptor (VDR) and oestrogen receptor (ER) genes play an important role in bone metabolism and the pathogenesis of osteoporosis. Little is known about the role of VDR and ER gene polymorphisms in rheumatoid arthritis (RA), although hormonal factors are highly involved in the evolution of autoimmune disorders. Objectives We assessed VDR BsmI, ER XbaI and ER PvuII polymorphisms in 50 RA patients as well as 50 healthy subjects. Methods Gene polymorphism was assessed in peripheral blood mononuclear cells taken from RA patients and healthy controls. After the PCR amplification of DNA isolated from these cells using specific primer pairs, DNA was digested with BsmI, PvuII and XbaI restriction enzymes. B versus b, X versus x and P versus p alleles, as well as homozygote and heterozygote genotypes were determined by agarose gel electrophoresis. Genotypes were then correlated with the bone density (assessed by DEXA), serum osteocalcin and urinary pyridinolin crosslink concentrations. Disease activity of RA was assessed by ESR and CRP. Results There is difference between VDR and ER polymorphisms in RA patients versus controls. A significantly higher percentage of RA patients carry the VDR Bb heterozygote genotype. XbaI and PvuII ER genotypes are also different in RA patients versus controls. There is a correlation between the VDR and ER genotypes, as well as bone density, biochemical markers and laboratory markers of RA activity. Conclusion It is likely, that VDR and ER polymorphisms are involved in bone metabolism as well as inflammatory events underlying RA.