Suppression of T lymphocyte activation in simulated microgravity

Immune dysfunction is encountered during spaceflight. Various aspects of spaceflight, including microgravity, cosmic radiation, and both physiological and psychological stress, may perturb immune function. We sought to understand the impact of microgravity alone on the cellular mechanisms critical to immunity. Clinostatic RWV bioreactors that simulate aspects of microgravity were used to analyze the response of human PBMC to polyclonal and oligoclonal activation. PHA responsiveness in the RWV bioreactor was almost completely diminished. IL-2 and IFN-$\gamma$ secretion was reduced whereas IL-1$\beta$ and IL-6 secretion was increased, suggesting that monocytes may not be as adversely affected by simulated microgravity as T cells. Activation marker expression (CD25, CD69, CD71) was significantly reduced in RWV cultures. Furthermore, addition of exogenous IL-2 to these cultures did not restore proliferation. Antigen specific T cell activation, including the mixed-lymphocyte reaction, tetanus toxoid responsiveness, and Borrelia activation of a specific T cell line, was also suppressed in the RWV bioreactor.^ The role of altered culture conditions in the suppression of T cell activation were considered. Potential reduced cell-cell and cell-substratum interactions in the RWV bioreactor may play a role in the loss of PHA responsiveness. However, PHA activation in Teflon culture bags that limit cell-substratum interactions was not affected. Furthermore, increasing cell-population density, and therefore cell-cell interactions, in the RWV cultures did not help restore PHA activation. However, placing PBMC within small collagen beads did partially restore PHA responsiveness. Finally, activation of purified T cells with crosslinked CD2/CD28 or CD3/CD28 antibody pairs, which does not require costimulation through cell-cell contact, was completely suppressed in the RWV bioreactor suggesting a defect internal to the T cell.^ Activation of both PBMC and purified T cells with PMA and ionomycin was unaffected by RWV culture, indicating that signaling mechanisms downstream of PKC activation and calcium flux are not sensitive to simulated microgravity. Furthermore, sub-mitogenic doses of PMA alone but not ionomycin alone restored PHA responsiveness of PBMC in RWV culture. Thus, our data indicate that during polyclonal activation in simulated microgravity, there is a specific dysfunction within the T cell involving the signaling pathways upstream of PKC activation. ^

DNA damage-induced Fas ligand expression by epidermal dendritic cells mediates UV-induced immune suppression of contact hypersensitivity

Exposure to UVB radiation induces local and systemic immune suppression, evidenced by inhibition of the contact hypersensitivity response (CHS). Epidermal dendritic cells, the primary antigen presenting cells responsible for the induction of CHS, are profoundly altered in phenotype and function by UVB exposure and possess UV-specific DNA damage upon migrating to skin-draining lymph nodes. Expression of the proapoptotic protein FasL has been demonstrated in both skin and lymph node cells following UVB exposure. Additionally, functional FasL expression has recently been demonstrated to be required in the phenomenon of UV-induced immune suppression. To test the hypothesis that FasL expression by DNA-damaged Langerhans cells migrating to the skin-draining lymph nodes is a crucial event in the generation of this phenomenon, mice were given a single 5KJ/m2 UV-B exposure and sensitized to 0.5% FITC through the exposed area. Dendritic cells (DC) harvested from skin-draining lymph nodes (DLN) 18 hours following sensitization by magnetic CD11c-conjugated microbeads expressed high levels of Iab, CD80 and CD86, DEC-205 and bore the FITC hapten, suggesting epidermal origin. Radioimmunoassay of UV-specific DNA damage showed that DC contained the vast majority of cyclobutane pyrimidine dimers (CPDs) found in the DLN after UVB and exhibited increased FasL mRNA expression, a result which correlated with greatly increased FasL-mediated cytotoxicity. The ability of DCs to transfer sensitization to naïve hosts was lost following UVB exposure, a phenomenon which required DC FasL expression, and was completely reversed by cutaneous DNA repair. Collectively, these results demonstrate the central importance of DNA damage-induced FasL expression on migrating dendritic cells in mediating UV-induced suppression of contact hypersensitivity. ^

The influence of contact pressure, moisture, and compression time on the performance of cotton anti-contamination clothing

The objectives of this research were (1) to study the effect of contact pressure, compression time, and liquid (moisture content of the fabric) on the transfer by sliding contact of non-fixed surface contamination to protective clothing constructed from uncoated, woven fabrics, (2) to study the effect of contact pressure, compression time, and liquid content on the subsequent penetration through the fabric, and (3) to determine if varying the type of contaminant changes the effect of contact pressure, compression time, and liquid content on the transfer by sliding contact and penetration of non-fixed surface contamination. ^ It was found that the combined influence of the liquid (moisture content of the fabric), load (contact pressure), compression time, and their interactions significantly influenced the penetration of all three test agents, sucrose- 14C, triolein-3H, and starch-14C through 100% cotton fabric. The combined influence of the statistically significant main effects and their interactions increased the penetration of triolein- 3H by 32,548%, sucrose-14C by 7,006%, and starch- 14C by 1,900%. ^

The influence of social connectedness and self-esteem on participant retention in a bi-ethnic longitudinal study

In prospective studies it is essential that the study sample accurately represents the target population for meaningful inferences to be drawn. Understanding why some individuals do not participate, or fail to continue to participate, in longitudinal studies can provide an empirical basis for the development of effective recruitment and retention strategies to improve response rates. This study examined the influence of social connectedness and self-esteem on long-term retention of participants, using secondary data from the “San Antonio Longitudinal Study of Aging” (SALSA), a population-based study of Mexican Americans (MAs) and European Americans (EAs) aged over 65 years residing in San Antonio, Texas. We tested the effect of social connectedness, self-esteem and socioeconomic status on participant retention in both ethnic groups. In MAs only, we analyzed whether acculturation and assimilation moderated these associations and/or had a direct effect on participant retention. ^ Low income, low frequency of social contacts and length of recruitment interval were significant predictors of non-completer status. Participants with low levels of social contacts were almost twice as likely as those with high levels of social contacts to be non-completers, even after adjustment for age, sex, ethnic group, education, household income, and recruitment interval (OR = 1.95, 95% CI: 1.26–3.01, p = 0.003). Recruitment interval consistently and strongly predicted non-completer status in all the models tested. Depending on the model, for each year beyond baseline there was a 25–33% greater likelihood of non-completion. The only significant interaction, or moderating, effect observed was between social contacts and cultural values among MAs. Specifically, MAs with both low social contacts and low acculturation on cultural values (i.e., placed high value on preserving Mexican cultural origins) were three and half times more likely to be non-completers compared with MAs in other subgroups comprised of the combination of these variables, even after adjustment for covariates. ^ Long term studies with older and minority participants are challenging for participant retention. Strategies can be designed to enhance retention by paying special attention to participants with low social contacts and, in MAs, participants with both low social contacts and low acculturation on cultural values. Minimizing the time interval between baseline and follow-up recruitment, and maintaining frequent contact with participants during this interval should also be is integral to the study design.^

Comparison of alternative methods of contact tracing in a syphilis control program

The purpose of this study was to compare the relative effectiveness of alternative methods of tracing named contacts of syphilis patients. A total of 236 contacts, identified by patients in two City of Houston Department of Health and Human Services clinics during the period April 1 through July 31, 1987, were studied. After contacts were grouped by sex and age, the proportion brought to examination by each of three methods, and by a combination of methods, was determined for each subgroup.^ The study found that 78.4% of all the 236 named sex contacts reported were located and brought to examination by the various methods of contact tracing and that 21.6% were missed. Of the 185 contacts examined, a combination of methods identified 47.7% of the cases, telephone contact, 28.6%, field contact, 16.9%, and patient referral, 11.8%.^ Of the 236 contacts reported, males made up 56.8% and females 43.2%. Contact tracing was more successful among females, with 81.4% of the 102 named female contacts, as compared to 76.1% of the 134 named male contacts being brought to examination. It is not known whether equal efforts were exerted in the follow-up of both male and female contacts. In both female and male subgroups, a combination of methods brought over 40% of sex contacts to examination. Telephone contact among females yielded 27.7% of the cases and field contact 18.1%, whereas in males, telephone contact identified 29.4% of the cases and field contact 15.7%. Patient referral was the least productive method in both sex groups, locating 12.8% in males as compared to 10.8% in females.^ On an age specific basis, a combination of methods was the most effective method in the 15-39 age group, whereas telephone contact was most effective in the 40-44 age group, and field contact in the 50-54 age group. Of all the methods of contact tracing, patient referral was the least productive in most age groups.^ Future studies of contact tracing should incorporate several important variables which were not examined in this study. ^