Normal telomere lengths in naive and memory CD4+ T cells in HIV type 1 infection: a mathematical interpretation.
To study CD4+ T cell productivity during HIV-1 infection, CD4+ T cell telomere lengths were measured. Cross-sectional and longitudinal analysis of HIV-1-infected individuals with CD4+ T cells counts >300 cells/mm3 showed normal average telomeric restriction fragment (TRF) length and normal shortening rates of CD45RA+ naive and CD45RO+ memory CD4+ T cells. These TRF data were interpreted in terms of CD4+ T cell production by means of a mathematical model. This model resolves previous criticisms arguing that the normal TRF length of CD4+ T cells in HIV-1 clinical latency is due to the killing of dividing CD4+ T cells by the virus. Only an increased priming rate of naive CD4+ T cells to become memory cells may elongate the average TRF length of memory CD4+ T cells, and may therefore mask the shortening effect of increased turnover in the CD4+ memory T cell compartment. The data are more compatible with the notion that during HIV-1 clinical latency the turnover of CD4+ T cells is not markedly increased, however, and that HIV-related interference with renewal from progenitors plays a role in CD4+ T cell depletion. In such a "limited renewal" scenario disease progression is no longer a consequence of markedly increased CD4+ T cell production.
Wolthers
K C
KC
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
Noest
A J
AJ
Otto
S A
SA
Miedema
F
F
De Boer
R J
RJ
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000648:ultrastructure*; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D008137:Longitudinal Studies; D008962:Models, Theoretical; D012150:Polymorphism, Restriction Fragment Length; D016615:Telomere