Regulatory T cell activity in primary and persistent Epstein-Barr virus infection.

Regulatory T cells (T(reg)) provide a balance to immune T cell activation thereby protecting the body from pathogen-induced immunopathology. Several persistent viruses induce T(reg) that subvert protective immune mechanisms and promote viral persistence. Epstein-Barr virus (EBV) generally infects children subclinically and persists thereafter, but primary infection in early adulthood may cause immunopathological damage manifest as infectious mononucleosis. In this study the role of T(reg) was investigated in acute infectious mononucleosis and healthy EBV seropositive donors. The proportion of CD4(+)CD25(high) T cells in blood from infectious mononucleosis patients was significantly lower than in seropositive donors (P = 0.05). Using the FOXP3 marker for T(reg) the same frequency and extra-follicular distribution of T(reg) was noted in infectious mononucleosis and control tonsils. Regulatory cytokines, interleukin (IL)-10 and transforming growth factor (TGF)-beta, were significantly raised in infectious mononucleosis compared to seropositive donor plasma (P = 0.0001, P = 0.0004 respectively) although levels of IL-10 peaked earlier in infectious mononucleosis than TGF-beta. Previous studies identified EBV latent membrane protein (LMP)-1-induced T(reg) activity [Marshall et al. (2003): J Immunol 170:6183-6189; Marshall et al. (2007): Brit J Haematol 139:81-89], and in this study a significant reduction in interferon-gamma production was found from infectious mononucleosis but not seropositive donor lymphocytes after stimulation with a recall antigen when LMP-1 peptide PRG was added (P = 0.03). It is possible that T(reg) are important in controlling primary EBV infection to a subclinical level in most cases and that infectious mononucleosis represents a failure of this protective mechanism.

Recruiting cancer patients to participate in motivating their relatives to quit smoking. A cancer control study of the Cancer and Leukemia Group B (CALGB 9072).

BACKGROUND: A diagnosis of cancer provides a teachable moment in which a physician can counsel or teach the patient. The Cancer and Leukemia Group B hypothesized that this teachable moment could also be used to encourage counseling of the patients' relatives who smoke. The authors' first study sought to determine the feasibility of such an intervention, the cooperation of the patients, and the compliance of relatives who were smokers. The long-range goal is to recruit by mail a large population of adult smokers into an intervention program and to assist them in quitting cigarette smoking. METHODS: Oncologists and their clinical research associates asked recently diagnosed cancer patients to identify their relatives who were smokers and assist in persuading them to quit. Consenting patients spoke to relatives and mailed them a personalized motivational leaflet along with a list of the benefits of quitting smoking. Intervention was continued only with relatives who were contacted in this manner. The participating physicians then wrote to the smokers, advising them to quit; enclosed with each physician's letter were the National Cancer Institute booklet "Clearing the Air," which is about quitting smoking, and a questionnaire determining "stage of change" (the stage of the smoker's inaction or action regarding quitting smoking). After 6 months, a postintervention questionnaire was mailed to the relatives. RESULTS: Written consent was obtained from 89% of 144 eligible patients solicited. Eighty percent of patients involved in the study contacted relatives. Sixty-three percent of contacted relatives returned the first questionnaire and 40% answered the second. Nine percent of all contacted relatives reported having quit smoking after the intervention. CONCLUSIONS: The intervention proved to be feasible and will lead to the next study, which will randomize relatives who smoke within a more intensive intervention over 12 months and compare the results with nonintervention controls.