Intracellular adhesion molecule-1 modulates beta-chemokines and directly costimulates T cells in vivo.

The potential roles of adhesion molecules in the expansion of T cell-mediated immune responses in the periphery were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the adhesion molecules intracellular adhesion molecule-1 (ICAM-1), lymphocyte function associated-3 (LFA-3), and vascular cell adhesion molecule-1 (VCAM-1) along with DNA immunogens, and we analyzed the resulting antigen-specific immune responses. We observed that antigen-specific T-cell responses can be enhanced by the coexpression of DNA immunogen and adhesion molecules ICAM-1 and LFA-3. Coexpression of ICAM-1 or LFA-3 molecules along with DNA immunogens resulted in a significant enhancement of T-helper cell proliferative responses. In addition, coimmunization with pCICAM-1 (and more moderately with pCLFA-3) resulted in a dramatic enhancement of CD8-restricted cytotoxic T-lymphocyte responses. Although VCAM-1 and ICAM-1 are similar in size, VCAM-1 coimmunization did not have any measurable effect on cell-mediated responses. These results suggest that ICAM-1 and LFA-3 provide direct T-cell costimulation. These observations are further supported by the finding that coinjection with ICAM-1 dramatically enhanced the level of interferon-gamma (IFN-gamma) and beta-chemokines macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and regulated on activation normal T-cell expression and secreted (RANTES) produced by stimulated T cells. Through comparative studies, we observed that ICAM-1/LFA-1 T-cell costimulatory pathways are independent of CD86/CD28 pathways and that they may synergistically expand T-cell responses in vivo.

Significance of unilateral submandibular gland excision on salivary flow in noncancer patients.

OBJECTIVES/HYPOTHESIS: Normal salivary flow is important for maintaining good oral hygiene. Lack of normal flow predisposes to an increased incidence of dental caries and symptomatic xerostomia. The submandibular glands are responsible for 70% of resting salivary flow. Removal of the submandibular gland is most commonly performed for sialolithiasis, chronic sialoadenitis, or as part of a neck dissection. The effect of unilateral gland resection for benign disease on resting salivary flow has not been well examined in the literature. STUDY DESIGN: Case controlled study involving patients who had undergone a unilateral submandibular gland resection matched with normal control subjects. METHOD: Stimulated and unstimulated salivary flow rates in surgical and control subjects were measured in a controlled setting. RESULTS: Unstimulated salivary flow rates were 0.805 mL/min in the control group and 0.405 mL/min in the surgical group (P = .01). Stimulated salivary flow rates were not significantly different between the two groups (P > .05). Fifty-seven percent of patients in the surgical group and 14% in the control group had xerostomia (P < .05). CONCLUSION: Unilateral submandibular gland excision results in a decreased rate of resting salivary flow and an increase in subjective xerostomia.