Immunosenescence is associated with presence of Kaposi's sarcoma in antiretroviral treated HIV infection

Unemori, Patricka; Leslie, Kieron S.a; Hunt, Peter W.b; Sinclair, Elizabethc; Epling, Lorriec; Mitsuyasu, Ronaldd; Effros, Rita B.d; Dock, Jeffreyd; Dollard, Sheila G.e; Deeks, Steven G.b; Martin, Jeffrey N.f; Maurer, Toby A.a

AIDS:
doi: 10.1097/QAD.0b013e3283601144
Clinical Science
Abstract

Objective: Some antiretroviral treated HIV-infected patients develop Kaposi's sarcoma despite long-term suppression of HIV replication. These Kaposi's sarcoma lesions are consistent with Kaposi's sarcoma observed in the elderly uninfected population (’classical Kaposi's sarcoma’). We investigated potential mechanisms for this phenomenon, focusing on measures of immune activation and T-cell senescence.

Design: We compared markers of immunosenescence, naive T cells, activation, and inflammation in CD4+ and CD8+ T cells from antiretroviral-treated participants with new-onset Kaposi's sarcoma (cases, n = 19) and from treated individuals without Kaposi's sarcoma (controls, n = 47).

Results: There was increased frequency of CD4+ and CD8+ T cells with an immunosenescence phenotype (CD57+ and CD28) in cases vs. controls (CD4+T cells: CD57+ 7.4 vs. 3.7%, P = 0.025; CD28 9.1 vs. 4.8%, P = 0.025; CD8+ T cells: CD57+ 41.5 vs. 27.7%, P = 0.003; CD28 60.5 vs. 51.3%, P = 0.041). Cases had lower proportions of naïve T cells (CD27+CD28+CD45RA+) in CD4+ (23.0 vs. 32.2%, P = 0.023) and CD8+ (11.3 vs. 20.7%, P < 0.001) T-cell compartments. CCR5 was more highly expressed in CD4+ (16.3 vs. 11.0%, P = 0.025), and CD8+ (43.1 vs. 28.3%, P <0.001) T-cell compartments in cases vs. controls. There was no difference in telomere length or telomerase activity in peripheral blood mononuclear cells, or in T-cell expression of activation markers (HLADR+CD38+).

Conclusion: Among antiretroviral-treated patients, increased frequencies of T cells with an immunosenescence phenotype and lower frequencies of naive T cells were associated with presence of Kaposi's sarcoma among effectively treated patients. These data suggest that certain immunologic perturbations –including those associated with aging – might be causally associated with development of Kaposi's sarcoma.

Author Information

aDepartment of Dermatology

bDepartment of Internal Medicine

cCenter for AIDS Research Core Immunology Laboratory, University of California, San Francisco

dDepartment of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California

eCenters for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, Georgia

fDepartment of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.

Correspondence to Patrick A. Unemori, San Francisco General Hospital, Ward 92, 1001 Potrero Avenue, San Francisco, CA 94110, USA. E-mail: Patrick_unemori@yahoo.com

Received 14 November, 2012

Revised 6 February, 2013

Accepted 11 February, 2013

© 2013 Lippincott Williams & Wilkins, Inc.