Role of CD8+ T Cells

Role of CD8+ T Cells

CD8+ T cells are critically important in the immune response to HIV. These cells attack and kill infected cells that are producing virus. Thus, vaccine efforts are directed toward eliciting or enhancing these killer T cells, as well as eliciting antibodies that will neutralize the infectivity of HIV.

CD8+ T cells also appear to secrete soluble factors that suppress HIV replication. Several molecules, including RANTES, MIP-1alpha, MIP-1beta, and MDC appear to block HIV replication by occupying the coreceptors necessary for many strains of HIV to enter their target cells. There may be other immune system molecules-including the so-called CD8 antiviral factor (CAF), the defensins (type of antimicrobials), and others yet undiscovered-that can suppress HIV replication to some degree.

Rapid Replication and Mutation of HIV

HIV replicates rapidly; several billion new virus particles may be produced every day. In addition, the HIV reverse transcriptase enzyme makes many mistakes while making DNA copies from HIV RNA. As a consequence, many variants or strains of HIV develop in a person, some of which may escape destruction by antibodies or killer T cells. Additionally, different strains of HIV can recombine to produce a wide range of variants.

During the course of HIV disease, viral strains emerge in an infected person that differ widely in their ability to infect and kill different cell types, as well as in their rate of replication. Scientists are investigating why strains of HIV from people with advanced disease appear to be more virulent and infect more cell types than strains obtained earlier from the same person. Part of the explanation may be the expanded ability of the virus to use other co-receptors, such as CXCR4.

Theories of Immune System Cell Loss in HIV Infection

Researchers around the world are studying how HIV destroys or disables CD4+ T cells, and many think that a number of mechanisms may occur simultaneously in an HIV-infected person. Data suggest that billions of CD4+ T cells may be destroyed every day, eventually overwhelming the immune system's capacity to regenerate.