Accessing Complexity: The Dynamics of Virus-Specific T Cell Responses

The cellular dynamics of the immune system are complex and difficult to measure. Access to this problematic area has been greatly enhanced by the recent development of tetrameric complexes of MHC class I glycoprotein + peptide (tetramers) for the direct staining of freshly isolated, antigen-specific CD8⁺ T cells. Analysis to date with both naturally acquired and experimentally induced infections has established that the numbers of virus-specific CD8⁺ T cells present during both the acute and memory phases of the host response are more than tenfold in excess of previously suspected values. The levels are such that the virus-specific CD8⁺ set is readily detected in the human peripheral blood lymphocyte compartment, particularly during persistent infections. Experimentally, it is now possible to measure the extent of cycling for tetramer ⁺CD8⁺ T cells during the acute and memory phases of the host response to viruses. Dissection of the phenotypic, functional, and molecular diversity of CD8⁺ T cell populations has been greatly facilitated. It is hoped it will also soon be possible to analyze CD4⁺ T cell populations in this way. Though these are early days and there is an enormous amount to be done, our perceptions of the shape of virus-specific cell-mediated immunity are changing rapidly.