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-l-infected individuals with CD4(+) T cells counts >300 cells/mm(3) 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.