Effects of testosterone and corticosterone on immunocompetence in the zebra finch

The original immunocompetence handicap hypothesis (ICHH) suggested that testosterone has a handicapping effect in males by both promoting the development of sexual signals and suppressing immune function. A modified version, the stress-linked ICHH, has recently proposed that testosterone is immunosuppressive indirectly by increasing production of corticosterone. To test both the original and stress-mediated versions of the ICHH, we implanted male zebra finches taken from lines selected for divergent maximum stress-induced levels of corticosterone (high, low and control) with either empty or testosterone-filled implants. Their humoral and cell-mediated immune responses were then assessed by challenge with diphtheria:tetanus vaccine and phytohemagglutinin respectively. We found no effect of the hormone manipulations on either PHA or tetanus antibody responses, but found a significant interaction between titers of both testosterone and corticosterone on diphtheria secondary antibody response; antibody response was greatest in individuals with high levels of both hormones. There was also a significant interactive effect between testosterone treatment group and corticosterone titer on body mass; the body mass of males in the elevated testosterone treatment group decreased with increasing corticosterone titer. These results suggest that, contrary to the assumption of the stress-mediated version of the ICHH, high plasma levels of corticosterone are not immunosuppressive, but are in fact immuno-enhancing in the presence of high levels of plasma testosterone. Equally, the central assumption of the ICHH that testosterone is obligately immunosuppressive is also not supported. The same individuals with the highest levels of both hormones and consequently the most robust antibody response also possessed the lowest body mass.

Assessment of delay in age-appropriate vaccination using survival analysis

 Assessment of delay in age-appropriate vaccination provides more information about timeliness of vaccination than up-to-date vaccination coverage. The authors applied survival analysis methods to data from a vaccination coverage survey among children aged 13–59 months conducted in Argentina in 2002. By age 19 months, 43% of children (95% confidence interval (CI): 40, 46) were vaccinated with the fourth dose of diphtheria, tetanus, and pertussis (DTP4). By age 13 months, 55% of children (95% CI: 52, 57) were vaccinated with measles-containing vaccine. By age 7 months, 33% of children (95% CI: 27, 40) were vaccinated with the third dose of hepatitis B. Compared with firstborn children, third children were more likely to be delayed for DTP4 (relative risk (RR) = 1.41, 95% CI: 1.22, 1.62), measles-containing vaccine (RR = 1.54, 95% CI: 1.32, 1.78), and the third dose of hepatitis B (RR = 1.31, 95% CI: 1.03, 1.67). Children whose caregivers had completed secondary school were less likely to be delayed for DTP4 (RR = 0.68, 95% CI: 0.52, 0.90) compared with those whose caregivers had not completed primary school. Survival analysis methods were helpful in measuring vaccine uptake and should be considered in future surveys when assessing delay in age-appropriate vaccination. Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved.

Foxp3 expression in macrophages associated with RENCA tumors in mice.

The transcription factor Foxp3 represents the most specific functional marker of CD4+ regulatory T cells (TRegs). However, previous reports have described Foxp3 expression in other cell types including some subsets of macrophages, although there are conflicting reports and Foxp3 expression in cells other than Treg is not well characterized. We performed detailed investigations into Foxp3 expression in macrophages in the normal tissue and tumor settings. We detected Foxp3 protein in macrophages infiltrating mouse renal cancer tumors injected subcutaneously or in the kidney. Expression was demonstrated using flow cytometry and Western blot with two individual monoclonal antibodies. Further analyses confirmed Foxp3 expression in macrophages by RT PCR, and studies using ribonucleic acid-sequencing (RNAseq) demonstrated a previously unknown Foxp3 messenger (m)RNA transcript in tumor-associated macrophages. In addition, depletion of Foxp3+ cells using diphtheria toxin in Foxp3DTR mice reduced the frequency of type-2 macrophages (M2) in kidney tumors. Collectively, these results indicate that tumor-associated macrophages could express Foxp3.