Assessing Family Strengths Using the Family Profile: Study to Validate and Evaluate Constructs Across Four Models of Family Functioning

The concurrent criterion-related validity of the Family Profile (FAMPRO) was investigated using the Family Adaptability and Cohesion Scales II (FACES II), the Self-Report Family Inventory (SFI), and the Family Assessment Device (FAD) as criterion measures . Further analysis was conducted through a principal component factor analysis with a varimax rotation and correlations with a Family Satisfaction Scale. The Family Profile is an easy-to-administer, -score, and -interpret instrument designed for use in family life education. It is a 35-item instrument that measures seven areas of family functioning: Family Fun, Family Decisions, Family Pride, Family Values, Family Caring, Family Communication, and Family Confidence. The total scores of the Family Profile had strong correlations with the total scores of the three criterion instruments. Additionally, the individual constructs of the Family Profile showed moderate to strong relationships with the corresponding subscales found in the criterion instruments. Factor analysis of the FAMPRO with this sample indicated that the most important factor explaining the largest portion of the variance is the ability of family members to display positive regard to one another in an open and warm manner. The Family Satisfaction Scale created for this project was moderately to strongly correlated with all of the Family Profile\u27s Subscales. The sample used for this study was taken from undergraduate Family and Human Development classes at Utah State University and had a total N of 194. This nonrandom sample was mostly young, single, and female. The religious preference for 80% of the sample was Mormon (LDS). While the sample limits generalization of the results, these preliminary results provide sufficient evidence to warrant further research using the Family Profile. Because the FAMPRO is easy to use and interpret, it holds promise as an effective tool for family life educators and clinicians alike

Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses

With increasing age, the ability to produce protective antibodies in response to immunization declines, leading to a reduced efficacy of vaccination in the elderly. To examine the effect of age on the cognate function of CD4 T cells, we have used a novel adoptive transfer model that allows us to compare identical numbers of antigen-specific naive T cells from young and aged TCR transgenic (Tg) donors. Upon transfer of aged donor CD4 T cells to young hosts, there was significantly reduced expansion and germinal center (GC) differentiation of the antigen-specific B cell population after immunization. This reduced cognate helper function was seen at all time points and over a wide range of donor cell numbers. In hosts receiving aged CD4 cells, there were also dramatically lower levels of antigen-specific IgG. These age-related defects were not due to defects in migration of the aged CD4 T cells, but may be attributable to reduced CD154 (CD40L) expression. Furthermore, we found that there was no difference in B cell expansion and differentiation or in IgG production when young CD4 T cells were transferred to young or aged hosts. Our results show that, in this model, age-related reductions in the cognate helper function of CD4 T cells contribute significantly to defects in humoral responses observed in aged individuals

Epitope-Specific Regulation of Memory Programming by Differential Duration of Antigen Presentation to Influenza-Specific CD8+ T Cells

SummaryMemory CD8+ T cells are programmed during the primary response for robust secondary responsiveness. Here we show that CD8+ T cells responding to different epitopes of influenza virus received qualitatively different signals during the primary response that altered their secondary responsiveness. Nucleoprotein (NP)-specific CD8+ T cells encountered antigen on CD40-licensed, CD70-expressing, CD103−CD11bhi dendritic cells (DCs) at later times in the primary response. As a consequence, they maintained CD25 expression and responded to interleukin-2 (IL-2) and CD27, which together programmed their robust secondary proliferative capacity and interferon-γ (IFN-γ)-producing ability. In contrast, polymerase (PA)-specific CD8+ T cells did not encounter antigen-bearing, CD40-activated DCs at later times in the primary response, did not receive CD27 and CD25 signals, and were not programmed to become memory CD8+ T cells with strong proliferative and cytokine-producing ability. As a result, CD8+ T cells responding to abundant antigens, like NP, dominated the secondary response

Prevention and Treatment of Influenza with Hyperimmune Bovine Colostrum Antibody

Background: Despite the availability of specific vaccines and antiviral drugs, influenza continues to impose a heavy toll on human health worldwide. Passive transfer of specific antibody (Ab) may provide a useful means of preventing or treating disease in unvaccinated individuals or those failing to adequately seroconvert, especially now that resistance to antiviral drugs is on the rise. However, preparation of appropriate Ab in large scale, quickly and on a yearly basis is viewed as a significant logistical hurdle for this approach to control seasonal influenza. Methodology/Principal Findings: In this study, bovine colostrum, which contains approximately 500 g of IgG per milking per animal, has been investigated as a source of polyclonal antibody for delivery to the respiratory tract. IgG and F(ab’)2 were purified from the hyperimmune colostrum of cows vaccinated with influenza A/Puerto Rico/8/34 (PR8) vaccine and were shown to have high hemagglutination-inhibitory and virus-neutralizing titers. In BALB/c mice, a single administration of either IgG or F(ab’)2 could prevent the establishment of infection with a sublethal dose of PR8 virus when given as early as 7 days prior to exposure to virus. Pre-treated mice also survived an otherwise lethal dose of virus, the IgG- but not the F(ab’)2-treated mice showing no weight loss. Successful reduction of established infection with this highly virulent virus was also observed with a single treatment 24 hr after virus exposure. Conclusions/Significance: These data suggest that a novel and commercially-scalable technique for preparing Ab fro

Newly generated CD4 T cells in aged animals do not exhibit age-related defects in response to antigen

Using a T cell receptor transgenic (TCR Tg) mouse model, we have shown that TCR Tg CD4 cells from aged mice retain a naive phenotype, but exhibit reduced proliferation and IL-2 production in response to the antigen compared with cells from young mice. We hypothesize that age-related decreases in T cell function may be partly related to the age of the T cells. Because thymic output is decreased with age, peripheral T cells in older individuals are likely to be older than those in younger individuals. To investigate this possibility, we have manipulated the age of CD4 T cells in the periphery of young and aged mice. The production of new T cells was induced by depleting peripheral CD4 T cells or by creating bone marrow chimeras. In both young and aged individuals where we induced the production of new T cells, these newly generated cells exhibited robust responses to antigen ex vivo and in vivo, exhibiting good expansion, IL-2 production, and cognate helper function. Our results suggest that age-related defects in response to antigenic stimulation, in part, are caused by the age of the CD4 T cells

The Biological Outcome of CD40 Signaling Is Dependent on the Duration of CD40 Ligand Expression: Reciprocal Regulation by Interleukin (IL)-4 and IL-12

CD40 ligand (CD154) expression on activated T cells can be separated into an early TCR-dependent phase, which occurs between 0 and 24 h after activation, and a later extended phase, which occurs after 24 h and is reciprocally regulated by the cytokines IL-4 and IL-12. IL-4 represses, whereas IL-12 sustains CD154 expression. Consistent with this, Th1, but not Th2, cells express CD154 for extended periods. Differences in the duration of CD154 expression have important biological consequences because sustained, but not transient, expression of CD154 on activated T cells can prevent B cell terminal differentiation. Thus, the differential ability of Th cells to sustain CD154 expression is an important part of their helper function and should influence the activities of other CD40-expressing cell types

Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus

A diverse T cell repertoire is essential for a vigorous immune response to new infections, and decreasing repertoire diversity has been implicated in the age-associated decline in CD8 T cell immunity. In this study, using the well-characterized mouse influenza virus model, we show that although comparable numbers of CD8 T cells are elicited in the lung and lung airways of young and aged mice after de novo infection, a majority of aged mice exhibit profound shifts in epitope immunodominance and restricted diversity in the TCR repertoire of responding cells. A preferential decline in reactivity to viral epitopes with a low naive precursor frequency was observed, in some cases leading to “holes” in the T cell repertoire. These effects were also seen in young thymectomized mice, consistent with the role of the thymus in maintaining naive repertoire diversity. Furthermore, a decline in repertoire diversity generally correlated with impaired responses to heterosubtypic challenge. This study formally demonstrates in a mouse infection model that naturally occurring contraction of the naive T cell repertoire can result in impaired CD8 T cell responses to known immunodominant epitopes and decline in heterosubtypic immunity. These observations have important implications for the design of vaccine strategies for the elderly

B Lymphocytes Are Required during the Early Priming of CD4\u3csup\u3e+\u3c/sup\u3e T Cells for Clearance of \u3cem\u3ePneumocystis\u3c/em\u3e Infection in Mice

B cells play a critical role in the clearance of Pneumocystis. In addition to production of Pneumocystis-specific Abs, B cells are required during the priming phase for CD4+ T cells to expand normally and generate memory. Clearance of Pneumocystis was found to be dependent on Ag specific B cells and on the ability of B cells to secrete Pneumocystis-specific Ab, as mice with B cells defective in these functions or with a restricted BCR were unable to control Pneumocystis infection. Because Pneumocystis-specific antiserum was only able to partially protect B cell–deficient mice from infection, we hypothesized that optimal T cell priming requires fully functional B cells. Using adoptive transfer and B cell depletion strategies, we determined that optimal priming of CD4+ T cells requires B cells during the first 2–3 d of infection and that this was independent of the production of Ab. T cells that were removed from Pneumocystis-infected mice during the priming phase were fully functional and able to clear Pneumocystis infection upon adoptive transfer into Rag1−/− hosts, but this effect was ablated in mice that lacked fully functional B cells. Our results indicate that T cell priming requires a complete environment of Ag presentation and activation signals to become fully functional in this model of Pneumocystis infection

Uneven Distribution of MHC Class II Epitopes within the Influenza Virus

The identification of T cell epitopes is crucial for the understanding of the host immune response during infection. While much is known about the MHC class I-restricted response following influenza virus infection of C57BL/6 mice, with over 16 CD8 epitopes identified to date, less is known about the MHC class II-restricted response. Currently, only a few I-Ab-restricted T helper epitopes have been identified. Therefore, several important questions remain about how many class II epitopes exist in this system and whether these epitopes are evenly distributed within the most abundant viral proteins. In order to address these questions, we analyzed the repertoire of epitopes that drive the CD4b T cell response to influenza virus infection in C57BL/6 (H-2b) mice. Using a panel of overlapping peptides from each of the viral proteins we show that approximately 20–30 epitopes drive the CD4 T cell response and that the majority of these peptides are derived from the NP and HA proteins. We were also able to demonstrate that vaccination with one of the newly identified epitopes, HA211–225/Ab, resulted in increased epitope-specific T cell numbers and a significant reduction in viral titers following influenza virus challenge