Effects of tick feeding on an early antigen-specific T cell response were studied by monitoring a clonotypic population of adoptively transferred T cell receptor (TCR) transgenic CD4 cells responding to a tick-associated antigen. When recipient mice were infested with pathogen-free Ixodes scapularis nymphs several days prior to T cell transfer and intradermal injection of soluble cognate antigen at the feeding site, the clonotypic CD4 cells gained the ability to express the Th2 effector cytokine IL-4. Notably, this effect was not only observed in BALB/c mice predisposed towards developing Th2 responses but also in B10.D2 mice predisposed towards Th1 responsiveness. Furthermore, tick feeding was able to superimpose IL-4 expression potential onto a strong Th1 response (indicated by robust IFN-gamma expression potential) elicited by immunization with a vaccinia virus expressing the cognate antigen. The magnitude to which tick feeding was able to programme IL-4 expression potential in CD4 cells was partially reduced in mice that had been previously exposed to pathogen-free tick nymphs 6 weeks earlier, as well as when the nymphs were infected with Borrelia burgdorferi. Intradermal injection of salivary gland extract programmed IL-4 expression potential similar to that of tick infestation, suggesting that IL-4 programming activity is contained within tick saliva.

As a tick feeds, its saliva induces innate and acquired immune responses in the host, including leucocyte infiltration into the bite site. Tick salivary glands produce molecules, however, that counteract many host defences against blood feeding. The effects of salivary-gland extracts (SGE) of Dermacentor andersoni and Ixodes scapularis on the expression of various adhesion molecules [E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)] by the sEND.1 cell line (which is based on cells from the subcutaneous tissue of mice) have now been investigated in vitro. The effects were found to differ with the tick species. The SGE of D. andersoni significantly down-regulated the expression of ICAM-1, whereas a similar extract prepared from I. scapularis significantly reduced the expression of P-selectin and VCAM-1. Tick salivary proteins therefore appear to have direct effects on adhesion-molecule expression, in addition to their previously established roles in down-regulating the pro-inflammatory cytokines that activate endothelial cells. It remains unclear exactly how the reduction of adhesion-molecule expression in the host's endothelial cells benefits the feeding tick but it may alter leucocyte migration to the bite site and/or reduce antigen presentation by the endothelial cells. It may also modulate the interactions between the host's leucocytes and any tick-borne pathogens, during initial infection of the endothelium.

Tick saliva contains molecules that modulate the haemostasis, pain/itch responses, wound healing and immune defences of the host. Using BALB/c mice that were each infested with 10 nymphs of Dermacentor andersoni Stiles (Acari: Ixodidae), an attempt has now been made to determine the influence of tick infestation on the expression of leucocyte adhesion molecules in the host. The ticks became fully engorged by the fourth to sixth day of infestation. On the fourth day of infestation, the results of flow cytometry indicated that 2% of the host's splenocytes were expressing high levels of CD49 (alpha4 integrin of VLA-4) and low levels of CD11a (alphaL subunit of the integrin LFA-1). By the eighth day of infestation, 30% of the hosts' splenocytes had this phenotype and were negative for the lineage markers CD3e (T-lymphocytes), DX5 (natural-killer cells of a BALB/c lineage), B220 (B-lymphocytes), CD11b (monocytes/macrophages, granulocytes, natural-killer cells, activated T-lymphocytes, and B-1 cells) and CD11c (myeloid and splenic dendritic cells). Histological examination of the spleens from infested mice revealed disruption of the white-pulp/red-pulp demarcations and the presence of a large number of basophilic normoblasts. The CD11a(lo) population of splenocytes from the tick-infested mice was positive for TER-119 but negative for CD3, B220, CD11b and Gr, confirming that the splenocytes were members of the erythroid lineage. These results indicate that, within 8 days of their initiation, the tick infestations induced extramedullary erythropoiesis in the spleens of their murine hosts.

Barriers to effective diagnostic testing for human immunodeficiency virus type 1 (HIV-1) infection can be reduced with simple, reliable, and rapid detection methods. Our objective was to determine the accuracy, sensitivity, and specificity of a new rapid, lateral-flow immunochromatographic HIV-1 antibody detection device. Preclinical studies were performed using seroconversion, cross-reaction, and interference panels, archived clinical specimens, and fresh whole blood. In a multicenter, prospective clinical trial, a four-sample matrix of capillary (fingerstick) whole-blood specimens and venous whole blood, plasma, and serum was tested for HIV-1 antibodies with the Efoora HIV rapid test (Efoora Inc., Buffalo Grove, IL) and compared with an enzyme immunoassay ( With the increasing availability of rapid tests for the detection of human immunodeficiency virus type 1 (HIV-1) antibodies, the screening of individuals for HIV infection is moving from laboratories to clinic-based settings (7). The early versions of these tests were neither easy to run nor particularly sensitive or specific (3, 19) Recent advances in the use of lateral-flow immunochromatographic strips and colloidal gold technology have allowed the development of rapid tests with very high sensitivity and specificity that are easy to run and can be used with whole blood (7,15). Rapid tests for the detection of antibodies to HIV in serum or plasma are commercially available and have been recently reviewed (7, 15).The potential public health benefits of rapid HIV testing are internationally recognized by the World Health Organization and in the United States by the Centers for Disease Control and Prevention (CDC), the Centers for Medicare and Medicaid Services, and the Food and Drug Administration (FDA) (15,20). There are at least four reasons to promote rapid HIV testing. First, a change in the paradigm of HIV counseling and testing would enhance a proactive role in HIV testing. According to the CDC client record database, only 25 to 43% of those patients who are ultimately determined to be positive and 33 to 48% of those who are negative return for their results if laboratory-based assays are performed. These rates have improved over the years (18) but are still unacceptably low. However, in clinical settings equipped with rapid HIV testing, patients can be present to observe the rapid testing, be informed of the result in Ͻ30 min, and be counseled immediately. Second, rapid HIV tests that can use whole-blood samples are much more efficient than enzyme immunoassay (EIA) testing in resource-limited settings where supplies (sterile needles, blood collection tubes, centrifuges, and electricity, etc.) are scarce and reporting mechanisms cumbersome (9, 21).