Increased Turnover of T Lymphocytes in HIV-1 Infection and Its Reduction by Antiretroviral Therapy
| Autor: | Keith Tung, Alan S. Perelson, Marc K. Hellerstein, Hiroshi Mohri, David D. Ho, Hurley, Denise Cesar, Bharat Ramratnam, Martin Markowitz, Rhonda G. Kost, Ruy M. Ribeiro, Leor S. Weinberger |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Time Factors Health Status Cell Gene Expression HIV Infections Apoptosis Lymphocyte proliferation CD8-Positive T-Lymphocytes Medical and Health Sciences Monocytes 0302 clinical medicine Immunology and Allergy Longitudinal Studies 0303 health sciences Mortality rate longitudinal study mechanisms of CD4+ T cell depletion Viral Load Middle Aged 3. Good health Infectious Diseases medicine.anatomical_structure deuterated glucose HIV/AIDS Original Article Female Infection Cell Division Adult T cell Immunology Biology 03 medical and health sciences Acquired immunodeficiency syndrome (AIDS) Clinical Research In vivo In Situ Nick-End Labeling medicine Humans 030304 developmental biology medicine.disease Antiretroviral therapy CD4 Lymphocyte Count Kinetics Ki-67 Antigen HIV-1 mathematical model CD8 030215 immunology |
| Zdroj: | The Journal of experimental medicine, vol 194, iss 9 The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.194.9.1277 |
| Popis: | The mechanism of CD4+ T cell depletion in human immunodeficiency virus (HIV)-1 infection remains controversial. Using deuterated glucose to label the DNA of proliferating cells in vivo, we studied T cell dynamics in four normal subjects and seven HIV-1–infected patients naive to antiretroviral drugs. The results were analyzed using a newly developed mathematical model to determine fractional rates of lymphocyte proliferation and death. In CD4+ T cells, mean proliferation and death rates were elevated by 6.3- and 2.9-fold, respectively, in infected patients compared with normal controls. In CD8+ T cells, the mean proliferation rate was 7.7-fold higher in HIV-1 infection, but the mean death rate was not significantly increased. Five of the infected patients underwent subsequent deuterated glucose labeling studies after initiating antiretroviral therapy. The lymphocyte proliferation and death rates in both CD4+ and CD8+ cell populations were substantially reduced by 5–11 weeks and nearly normal by one year. Taken together, these new findings strongly indicate that CD4+ lymphocyte depletion seen in AIDS is primarily a consequence of increased cellular destruction, not decreased cellular production. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|