In vivo TCR Signaling in CD4(+) T Cells Imprints a Cell-Intrinsic, Transient Low-Motility Pattern Independent of Chemokine Receptor Expression Levels, or Microtubular Network, Integrin, and Protein Kinase C Activity

Intravital imaging has revealed that T cells change their migratory behavior during physiological activation inside lymphoid tissue. Yet, it remains less well investigated how the intrinsic migratory capacity of activated T cells is regulated by chemokine receptor levels or other regulatory elements. Here, we used an adjuvant-driven inflammation model to examine how motility patterns corresponded with CCR7, CXCR4, and CXCR5 expression levels on ovalbumin-specific DO11.10 CD4(+) T cells in draining lymph nodes. We found that while CCR7 and CXCR4 surface levels remained essentially unaltered during the first 48-72 h after activation of CD4(+) T cells, their in vitro chemokinetic and directed migratory capacity to the respective ligands, CCL19, CCL21, and CXCL12, was substantially reduced during this time window. Activated T cells recovered from this temporary decrease in motility on day 6 post immunization, coinciding with increased migration to the CXCR5 ligand CXCL13. The transiently impaired CD4(+) T cell motility pattern correlated with increased LFA-1 expression and augmented phosphorylation of the microtubule regulator Stathmin on day 3 post immunization, yet neither microtubule destabilization nor integrin blocking could reverse TCR-imprinted unresponsiveness. Furthermore, protein kinase C (PKC) inhibition did not restore chemotactic activity, ruling out PKC-mediated receptor desensitization as mechanism for reduced migration in activated T cells. Thus, we identify a cell-intrinsic, chemokine receptor level-uncoupled decrease in motility in CD4(+) T cells shortly after activation, coinciding with clonal expansion. The transiently reduced ability to react to chemokinetic and chemotactic stimuli may contribute to the sequestering of activated CD4(+) T cells in reactive peripheral lymph nodes, allowing for integration of costimulatory signals required for full activation.

A novel CYP17A1 deletion causes a functional knockout of the steroid enzyme 17-hydroxylase and 17,20-lyase in a Turkish family and illustrates the precise role of the CYP17A1 gene

A novel homozygous long-range deletion of the CYP17A1 gene abolished protein expression and caused the severest form of 17-hydroxylase deficiency in one kindred of a Turkish family. The affected subjects presented with 46,XY sex reversal and 46,XX lack of pubertal development as well as severe hypertension.

Ingestion rate and egg production of copepods collected in the Turkish Strait during Bilim 2 cruise in April 2008

The copepod Ingestion on ciliates, phytoplankton and the copepod production dataset is based on samples taken during April 2008 in Dardanelles Straits, Marmara Sea and Bosporus Straits at the third priority stations. These experiments were set up according to DoW of Sesame project. Copepods for the experiments were obtained with slow non-quantitative tows from the upper 50 m layer of the water column using 200 µm mesh size nets fitted with a large non-filtering cod end. For the grazing experiments we used the following copepod species: Centropages typicus and Acartia clausi according to the relevant reference (Bamstedt et al. 2000). Copepod clearance rates on ciliates were calculated according to Frost equations (Frost 1972). Ingestion rates were calculated by multiplying clearance rates by the initial standing stocks (Bamstedt et al. 2000). Egg production rates of the dominant calanoid copepods were determined by incubation of fertilised females (eggs/female/day) collected in the 0-20m layer. Copepod egg production was measured for the copepods Centropages typicus and Acartia clausi. On board experiments for the estimation of copepod egg production were taken place. For the estimation of copepod production (mg/m**2/day), lengths (copepods and eggs) were converted to body carbon (Hopcroft et al., 1998) and production was estimated from biomass and weight-specific egg production rates, by assuming that those rates are representative for juvenile specific growth rates (Berggreen et al., 1988).

Abundance of microplankton in the Turkish Strait during Bilim 2 cruise in April 2008

The HCMR_SES_UNLUATA_CRUISES_TURKISH_STRAITS_CHLA & PP dataset was obtained on samples taken from 5 stations in the Dardanelles Straits, Marmara Sea and Bosporus Straits. These experiments were set up according to DoW of SESAME project. Microplankton species composition analysis was performed according to the Utermöhl's (1958) inverted microscope method. Samples for the identification and enumeration of larger phytoplankton cells (>5?m), were preserved in alkaline Lugol's solution.