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Persistent alterations in the T-cell repertoires of HIV-1-infected and at-risk uninfected men

Killian, M Scotta; Monteiro, Joanitab; Matud, Josea; Hultin, Lance Ea; Hausner, Mary Anna; Yang, Otto Oc; Gregersen, Peter Kb; Detels, Rogerd; Giorgi, Janis Va; Jamieson, Beth Da

Basic Science

Objective: We examined the association between immunogenic exposure and T-cell receptor (TCR) diversity to more clearly assess the impact of HIV-1 infection on the T-cell repertoire.

Methods: To estimate the extent of T-cell clonality attributable to HIV-1 infection, we evaluated T-cell repertoires in low-risk and at-risk seronegative men and HIV-1 seropositive men by assessment of T-cell receptor beta-chain (TCRβ) complimentary determining region 3 (CDR3) lengths.

Results: The frequency of T-cell clonality in both HIV-1 infected and at-risk uninfected men was elevated in comparison to low-risk uninfected men. Among low-risk and at-risk seronegative, and HIV-1 seropositive men, clonal expansions were present in 3, 8, and 10% of CD4+ CDR3 lengths, and 18, 22, and 28% of CD8+ CDR3 lengths respectively. In addition, the longitudinal conservation of clonal expansions was observed in at-risk seronegative men. Based on comparisons to at-risk seronegative men, we estimate that at-risk seropositive men with chronic HIV-1 infection exhibit a 27% increase in the number of expanded CD8+ CDR3 lengths.

Conclusion: These findings provide an approximation of the magnitude of the T-cell response in individuals undergoing chronic HIV-1 infection and demonstrate a significant association between the history of immunogenic challenge and the magnitude of clonality within the T-cell repertoire. In addition, these findings underscore the necessity of selecting controls with similar antigenic exposure histories when investigating T-cell dynamics in HIV-infected individuals.

From the aDivision of Hematology/Oncology and cDivision of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, the dDepartment of Epidemiology, UCLA School of Public Health, University of California, Los Angeles, California and the bDivision of Biology and Human Genetics, Department of Internal Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, New York, USA.

Note: Professor Janis V. Giorgi passedaway on 30 May 2000.

Correspondence to Dr B. Jamieson, UCLA Cellular Immunology and Cytometry, Room 12-240, Factor Building, UCLA, 650 Charles E. Young Drive, Los Angeles, CA 90095, USA.

Tel: +1 310 206 7287; fax: +1 310 794 2145; e-mail address: jamieson@mednet.ucla.edu

Received: 29 May 2003; revised: 28 July 2003; accepted: 19 August 2003.

© 2004 Lippincott Williams & Wilkins, Inc.