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Cara Wilson, MD

Professor, Divisions of Infectious Diseases and Clinical Immunology
 

 

Phone: 303-724-4922
E-mail: Cara.Wilson@ucdenver.edu
Address: 12700 E. 19th Avenue Box B168
Aurora, CO 80045

Medical School
University of Virginia School of Medicine,
Charlottesville VA (1984-88)

 

Residency
Internal Medicine, Johns Hopkins Hospital
Baltimore MD

Fellowship
Infectious Diseases, Massachusetts General Hospital
Boston MA (1991-95)

 

Role of Dendritic Cell Activation in HIV-1 pathogenesis. HIV-1 infection is marked by progressive CD4+ T cell destruction, HIV-specific CD4+ and CD8+ T cell dysfunction, and chronic immune activation. Although HIV-1-specific T cell responses are often generated early in infection, they progressively lose the ability to suppress viral replication in vivo. The cumulative result of these immune defects is AIDS in the majority of infected individuals. Dendritic cells (DCs) are specialized antigen presenting cells (APCs) that bridge the gap between innate and adaptive immunity. They respond to viral pathogens by becoming activated or "mature", a process that leads to induction of pathogen-specific T cell responses and production of antiviral cytokines, such as type I IFNs. In the setting of HIV-1 infection, we have observed that blood plasmacytoid (pDCs) and myeloid (mDCs) DCs are depleted in number, dysfunctional, and show atypical patterns of activation. Importantly, these DC abnormalities failed to normalize after 6 months of suppression of HIV-1 replication with highly active antiretroviral therapy (HAART). Although defective antigen presenting cell function has been implicated in HIV-1 pathogenesis, the impact of HIV-associated BDC abnormalities on the extent of T cell function and immune recovery before and after HAART have not been fully evaluated. The Wilson lab is interested in studying both in vivo and in vitro the factors that influence HIV-associated DC activation, and in turn, how this activation influences activation and function of T cells.

HIV-specific T cell function in Acute and Recent HIV-1 Infection. Acutely and recently HIV-1-infected individuals who received suppressive antiviral therapy (highly active antiretroviral therapy, HAART) early in their disease course often develop strong HIV-1 Gag-specific CD4+ T cell proliferative response, a type of cellular immune response that is generally absent in chronically HIV-infected individuals with progressive disease. Furthermore, many acutely infected/treated patients are able to control viral replication and maintain low viral loads off of therapy following a series of structured treatment interruptions (STIs). This control of viral replication is temporally associated with increasing HIV-specific cytotoxic T lymphocyte (CTL) responses. These interesting findings suggest that there might be a relationship between HIV-specific helper T lymphocyte (HTL) and CTL responses and the ability to control viral replication in vivo in the acute infection setting, and even that strong HIV-specific cellular immune responses might predict immunologic control of viral replication. However, the frequency, diversity of epitope recognition, and the function of HIV-1-specific CD4+ T cells in acutely-infected, treated individuals has not been fully evaluated. Furthermore, the relationship between HTL and CTL responses in this setting, their ability to exert immune selection pressure on replicating HIV-1, and their role in controlling viremia in this clinical setting has likewise not been prospectively and comprehensively studied. Therefore, these proposed studies are critical in order to first determine whether HIV-specific CD4+ and CD8+ T cells play a role in viral suppression in the acute infection setting and after STI, and secondly to understand which characteristics of these cells are important in mediating this control.

 

1) Wilson CC, Palmer B, Southwood S, Sidney J, Higashimoto Y, Appella E, Chesnut R, Sette A, Livingston BD. Identification and antigenicity of broadly cross-reactive and conserved human immunodeficiency virus type 1-derived helper t-lymphocyte epitopes. J Virol 2001;75(9):4195-207.

2) Stubbs AC, Martin KS, Coeshott C, Skaates SV, Kuritzkes DR, Bellgrau D, Franzusoff A, Duke RC, Wilson CC. Whole recombinant yeast vaccine activates dendritic cells and elicits protective cell-mediated immunity. Nat Med 2001;7:625-9.

3) Stubbs AC, Wilson CC. Recombinant yeast as a vaccine vector for the induction of cytotoxic T-lymphocyte responses. Curr Opin Mol Ther. 2002 Feb;4(1):35-40.

4) Palmer, B., Boritz, E., Blyveis, N., and C.C. Wilson. Discordance between frequency of HIV-1-specific IFN-γ-producing CD4+ T cells and HIV-1-specific lymphoproliferation in HIV-1-infected subjects with active viral replication. J Virol 2002;76(12):5925-5936.

5) MA. Barron, N Blyveis, B Palmer, S MaWhinney, and C.C. Wilson. Defects in Number and Surface Expression of Co-stimulatory Molecules in Both CD11c+ and CD11c- Blood DCs in HIV-1-Infected Individuals. Journal of Infectious Diseases 2003, Jan. 1; 187(1):26-37.

6) Eli Andrew Boritz, Brent Palmer, Brian Livingston, and Cara C. Wilson. Diversity of HIV-p24-specific CD4+ T Cell Clones in the setting of Immune Reconstitution after Highly Active Antiretroviral Therapy (HAART). Journal of Immunology 2003, Jan. 15; 170(2):1106-16.

7) Newman, M.J., McKinney, D., Chesnut, R., Sette, A., Wilson, C., and Livingston, B. Design and construction of T-lymphocyte epitope-based therapeutic HIV-1 vaccines. Clinical and Applied Immunology Reviews. 2003. 3:157-166.

8) Cara C. Wilson, Denise McKinney, Michelle Anders, Samantha MaWhinney, Jeri Forster, Claire Crimi, Scott Southwood, Alessandro Sette, Robert Chesnut, Mark J. Newman and Brian D. Livingston. Development of a DNA Vaccine Designed to Induce Cytotoxic T Lymphocyte Responses to Multiple Conserved Epitopes in HIV-1. J Immunol. 2003, Nov 15;171(10):5611-23.

9) Brent Palmer, Eli Boritz, and Cara Wilson. Effects of sustained HIV-1 plasma viremia on HIV-1-specific CD4+ T cell maturation and function. J Immunology 2004, 172: 3337-3347.

10) Denise M. McKinney, Rhonda Skvoretz, Brian D. Livingston, Cara C. Wilson, Michelle Anders, Robert W. Chesnut, Alessandro Sette and Mark J. Newman. Recognition of variant HIV-1 epitopes from diverse viral subtypes by vaccine-induced CTL. J Immunol. 2004 Aug 1;173(3):1941-50.

11) Eli Boritz, Brent E. Palmer, and Cara C. Wilson. Human Immunodeficiency Virus Type 1-specific CD4+ T Cells that Proliferate In Vitro Detected from Most Viremic Subjects and Associated with Lower Plasma HIV-1 Loads. J. Virology 2004, Nov;78(22):12638-46.

12) McCarter MD, Clarke J, Richter D, Wilson CC. Melanoma skews dendritic cells to facilitate a T helper 2 profile. Surgery. 2005, 138:321-8.

13) Brent E. Palmer, Naomi Blyveis, Andrew P. Fontenot, and Cara C. Wilson. Functional and phenotypic characterization of CD57+ T cells and their association with HIV-1-induced T cell dysfunction. J Immunol. 2005, 175(12):8415-23.

14) John R. Koeppe, Thomas P. Campbell, Richard Rapaport, and Cara C. Wilson. HIV-1 specific CD4+ T cell responses are not associated with significant viral epitope variation in persons with persistent plasma viremia. J AIDS. 2006 41(2):140-8.

15) Michelle A. Barron, Naomi Blyveis, Samuel C. Pan, and Cara C. Wilson. Human Dendritic Cell Interactions with Whole Recombinant Yeast: Implications for HIV-1 Vaccine Development. J Clin Immunology. 2006, May 13.

16) Eli Boritz, Eric L. Rapaport, Thomas P. Campbell, John R. Koeppe, and Cara C. Wilson. CD4+ T Cell Targeting of HIV-1 Peptide Sequences Present In Vivo during Chronic, Progressive HIV-1 Disease. Virology 2006, Dec. 12.

R01 AI065275 (C. Wilson, PI)
Source: NIH/NIAID
HIV-related blood dendritic cell dysfunction
Role: Principal Investigator
The goal of this program is to study interactions between HIV and blood denritic cells, and how these interactions impact HIV-1 disease progression.

P01 AI55356 (E. Connick, Program P.I.)
Source: NIH/NIAID
Immunopathogenesis of Acute HIV-1 Infection
Role: Principal Investigator for Project 3
Project 3 entitled "Role of HIV-1-specific Cellular Immune Responses in Mediating Virologic Control in Early HIV-1 Infection".
The goal of this program is to study the pathogenesis and therapy of individuals with primary HIV infection.