T-cell homeostasis, competition, and drift: AIDS as HIV-accelerated senescence of the immune repertoire.
The observation that the density of CD8+ T-lymphocytes increases as the density of CD4+ T-cells declines in adult HIV-1/AIDS patients, together with evidence that the total density of T-cells is regulated (homeostasis) has led to the suggestion that competition between lineages, and classes of T-cells contributes to the pathology of HIV. We use a mathematical model of the interactions between populations of T-cells, HIV, and other parasites to explore the effects of T-cell homeostasis and competition on the progression to AIDS. We demonstrate that as a consequence of parasite-mediated T-cell replication, of competition within and between different T-cell clones, and random processes (T-cell drift), some CD4+ lineages will be represented by relatively few cells, dearths, and some lineages may be lost, leaving holes in the immune repertoire. By killing CD4+ T-lymphocytes, HIV accelerates the rate at which these dearths and holes accumulate and leads to an early breakdown of the immune control of HIV and other parasites, AIDS. When this model allows for intense, but not complete, competition between the CD4+ and CD8+ T-cell populations, it can account for most of the features of an HIV-1 infection in adults, including the gradual decline in CD4+ T-cell densities and concomitant increase in HIV density, as well as the variability in time from infection to AIDS and the decline in the time from infection to AIDS in older patients.
Mittler
J E
JE
Department of Biology, Emory University, Atlanta, Georgia, USA.
Levin
B R
BR
Antia
R
R
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D000328:Adult; D000367:Age Factors; D000818:Animals; D001419:Bacteria / Q000276:immunology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003198:Computer Simulation; D003429:Cross Reactions; D018450:Disease Progression; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D009010:Monte Carlo Method; D013601:T-Lymphocytes / Q000276:immunology*; D014780:Viruses / Q000276:immunology