Publications

Tissue-resident memory (T) CD8 T-cells are non-recirculating, long-lived cells housed in tissues that can confer protection against mucosal pathogens. Human immunodeficiency virus-1 (HIV-1) is a mucosal pathogen and the gastrointestinal tract is an important site of viral pathogenesis and transmission. Thus, CD8 T cells may be an important effector subset for controlling HIV-1 in mucosal tissues. This study sought to determine the abundance, phenotype, and functionality of CD8 T cells in the context of chronic HIV-1 infection. We found that the majority of rectosigmoid CD8 T-cells were CD69CD103S1PR1 and T-betEomesodermin, indicative of a tissue-residency phenotype similar to that described in murine models. HIV-1-specific CD8 T responses appeared strongest in individuals naturally controlling HIV-1 infection. Two CD8 T subsets, distinguished by CD103 expression intensity, were identified. CD103 CD8 T primarily displayed a transitional memory phenotype and contained HIV-1-specific cells and cells expressing high levels of Eomesodermin, whereas CD103 CD8 T primarily displayed an effector memory phenotype and were Eomesodermin. These findings suggest a large fraction of CD8 T-cells housed in the human rectosigmoid mucosa are tissue-resident and that T contribute to the anti-HIV-1 immune response. Further exploration of CD8 T will inform development of anti-HIV-1 immune-based therapies and vaccines targeted to the mucosa.

BACKGROUND

Individuals with severe mental illness (e.g., schizophrenia, bipolar disorder) die 10-25 years earlier than the general population, primarily from premature cardiovascular disease (CVD). Contributing factors are complex, but include systemic-related factors of poorly integrated primary care and mental health services. Although evidence-based models exist for integrating mental health care into primary care settings, the evidence base for integrating medical care into specialty mental health settings is limited. Such models are referred to as "reverse" integration. In this paper, we describe the application of an implementation science framework in designing a model to improve CVD outcomes for individuals with severe mental illness (SMI) who receive services in a community mental health setting.

METHODS

Using principles from the theory of planned behavior, focus groups were conducted to understand stakeholder perspectives of barriers to CVD risk factor screening and treatment identify potential target behaviors. We then applied results to the overarching Behavior Change Wheel framework, a systematic and theory-driven approach that incorporates the COM-B model (capability, opportunity, motivation, and behavior), to build an intervention to improve CVD risk factor screening and treatment for people with SMI.

RESULTS

Following a stepped approach from the Behavior Change Wheel framework, a model to deliver primary preventive care for people that use community mental health settings as their de facto health home was developed. The CRANIUM (cardiometabolic risk assessment and treatment through a novel integration model for underserved populations with mental illness) model focuses on engaging community psychiatrists to expand their scope of practice to become responsible for CVD risk, with significant clinical decision support.

CONCLUSION

The CRANIUM model was designed by integrating behavioral change theory and implementation theory. CRANIUM is feasible to implement, is highly acceptable to, and targets provider behavior change, and is replicable and efficient for helping to integrate primary preventive care services in community mental health settings. CRANIUM can be scaled up to increase CVD preventive care delivery and ultimately improve health outcomes among people with SMI served within a public mental health care system.