Platelet-mediated modulation of adaptive immunity: unique delivery of CD154 signal by platelet-derived membrane vesicles.

Although mounting evidence indicates that platelets participate in the modulation of both innate and adaptive immunity, the mechanisms by which platelets exert these effects have not been clearly defined. The study reported herein uses a previously documented adoptive transfer model to investigate the ability of platelet-derived membrane vesicles to communicate activation signals to the B-cell compartment. The findings demonstrate for the first time that platelet-derived membrane vesicles are sufficient to deliver CD154 to stimulate antigen-specific IgG production and modulate germinal center formation through cooperation with responses elicited by CD4(+) T cells. The data are consistent with the hypothesis that platelets modulate inflammation and adaptive immunity at sites distant from the location of activation and that platelet-derived membrane vesicles are sufficient to mediate the effect.

The fibronectin attachment protein of bacillus Calmette-Guerin (BCG) mediates antitumor activity.

PURPOSE: The receptor responsible for the attachment of bacillus Calmette-Guerin (BCG) to fibronectin, fibronectin attachment protein (FAP), has been cloned. Studies targeting FAP as an inducer of immunity in mycobacterial infections suggest that FAP is a highly immunogenic protein. In light of these findings and the need to find effective alternatives to BCG treatment for bladder cancer, we tested the ability of FAP to induce antitumor activity. MATERIALS AND METHODS: The ability of FAP to bind to bladder tumor cells and the bladder wall was established using (125)I-FAP. For testing antitumor activity in vivo, mice were catheterized and 5 x 10(4) MB-49 bladder tumor cells were implanted orthotopically on day 0. Test groups were treated with PBS only, FAP, or BCG on day 1 and day 8. A subset of mice was preimmunized with FAP prior to treatment. RESULTS: FAP was observed to bind to bladder tumor cells in a fibronectin-dependent manner. Attachment of FAP within the bladder followed the pattern established for BCG binding. Antitumor studies showed a significant reduction in tumor growth in FAP-treated mice that had been preimmunized with FAP. Tumor growth was not inhibited in naïve mice treated with FAP. Dose-response studies showed that FAP-induced antitumor activity is dose dependent, and experiments comparing BCG with FAP showed equivalent antitumor effects. In vitro experiments showed antigen-specific lymphocyte proliferation and a cytokine profile indicative of Th-1 polarization of the FAP-induced immune response. CD8+ T cells and natural killer cells were found to be required for the FAP-induced antitumor response. CONCLUSIONS: FAP is an effective antitumor agent that inhibits tumor growth at a level equivalent to that observed for BCG. This protein may thus provide an alternative to BCG for treatment of superficial bladder cancer.

Correlation of skeletal maturation stages determined by cervical vertebrae and hand-wrist evaluations.

The aim of this study was to assess the correlation between the Fishman maturation prediction method (FMP) and the cervical vertebral maturation (CVM) method for skeletal maturation stage determination. Hand-wrist and lateral cephalograms from 79 subjects (52 females and 27 males) were used. Hand-wrist radiographs were analyzed using the FMP to determine skeletal maturation level (advanced, average, or delayed) and stage (relative position of the individual in the pubertal growth curve). Cervical vertebrae (C2, C3, and C4) outlines obtained from lateral cephalograms were analyzed using the CVM to determine skeletal maturation stage. Intraexaminer reliability (Intraclass correlation coefficient [ICC]) for both methods was calculated from 10 triplicate hand-wrist and lateral cephalograms from the same patients. An ICC coefficient of 0.985 for FMP and an ICC of 0.889 for CVM were obtained. A Spearman correlation value of 0.72 (P < .001) was found between the skeletal maturation stages of both methods. When the sample was subgrouped according to skeletal maturation level, the following correlation values were found: for early mature adolescents 0.73, for average mature adolescents 0.70, and for late mature adolescents 0.87. All these correlation values were statistically different from zero (P < .024). Correlation values between both skeletal maturation methods were moderately high. This may be high enough to use either of the methods indistinctively for research purposes but not for the assessment of individual patients. Skeletal level influences the correlation values and, therefore, it should be considered whenever possible.

Platelet-mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments.

Platelets are highly reactive components of the circulatory system with well-documented hemostatic function. Recent studies extend platelet function to modulation of local inflammatory events through the release of chemokines, cytokines, and a number of immunomodulatory ligands, including CD154. We hypothesized that platelet-derived CD154 modulates adaptive immunity. The data reported herein demonstrate that platelets, via CD154, induce dendritic cell maturation, B cell isotype switching, and augment CD8(+) T cell responses both in vitro and in vivo. Platelet transfusion studies demonstrate that platelet-derived CD154 alone is sufficient to induce isotype switching and augment T lymphocyte function during viral infection, leading to enhanced protection against viral rechallenge. Additionally, depletion of platelets in normal mice results in decreased antigen-specific antibody production.