Regulatory T Cells and HIV Disease

Tulane University Of Louisiana, New Orleans LA

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): Cell-mediated immune responses directed at HIV are critical determinants of viral containment. Hallmarks of chronic HIV infection are immune hyper activation and inefficient HIV-specific T lymphocyte responses. Emerging evidence suggests that FOXP3+-expressing CD4+CD25+ regulatory T lymphocytes (Treg) diminish tumor-specific and pathogen-specific CD4+ and CD8+ T-cell mediated responses. Detailed studies by our lab revealed that Treg foster immune privilege in human ovarian cancer, where tumor-associated Treg number predicted survival. There is recent evidence suggesting that Treg inhibit HIV-specific immunity. Based on work by us and others, we hypothesize that Treg activity contributes to immune failure in chronic HIV infection. Further, successful viral suppression with antiviral therapy may require a concomitant Treg reduction. The proposed research will include a comprehensive study of Treg function in peripheral blood in relation to HIV-specific immunity and HIV viral replication among chronically HIV-infected, treatment naive individuals. Enrollment will be conducted at the Ryan White and state funded HIV Outpatient Clinic in New Orleans where over a third of HIV cases present late to care and commonly develop AIDS within the first year after diagnosis. We aim to test the hypothesis that increased Treg numbers and function in blood predict poor HIV-specific immunity and poor virologic control in treatment naive patients with chronic HIV. The cohort will be followed longitudinally in order to test if changes in Treg function and number during HAART predict the magnitude or durability of virologic and immunologic responses. Our long-term goal is to understand the effects of HAART on Treg function and how such changes relate to virologic control. Insights may lead to novel immune-based therapies, and means to predict the clinical response to HAART. This research will provide a foundation for the candidate to develop the multidisciplinary skills needed to establish herself as an independent clinical investigator in the field of HIV immunology. This work and training will be supported by and conducted under the supervision of Dr. Tyler Curiel, an expert in human immunology and Treg function. [unreadable] [unreadable] [unreadable] [unreadable]