In vitro human memory CD8 T cell expansion in response to cytomegalovirus requires CD4+ T cell help.
Requirements for human memory CD8(+) T cell expansion are incompletely understood. We found that human cytomegalovirus (HCMV) induced expansion of memory CD8(+) T cells in vitro without requiring intracellular viral peptide synthesis. Peptide-major histocompatibility complex class I tetramer binding confirmed expansion of cells with HCMV-peptide specificity. Expansion of memory CD8(+) T cells was completely dependent on the presence and function of CD4(+) T cells, whose "help" also could be induced by exposure to irrelevant antigen. Recombinant interleukin (IL)-2 or IL-15 could substitute for help provided by CD4(+) T cells, whereas CD8(+) T cell expansion was blocked by anti-IL-2 but not anti-IL-15 antibody. Human memory CD8(+) T cells expand dramatically in vitro in response to cross-presentation of HCMV antigens, and, in contrast to observations made in murine systems, this proliferation was critically dependent on CD4(+) T cells that provide essential IL-2. Thus, in humans, cross-presentation and expansion of memory CD8(+) T cells may be compromised in disease states that result in deficits in CD4(+) T cell numbers or function, such as may be seen in human immunodeficiency virus type 1 infection.
Center For AIDS Research and Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Janelle R
JR
Salkowitz
Scott F
SF
Sieg
Clifford V
CV
Harding
Michael M
MM
Lederman
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D013745:Tetanus Toxoid / Q000276:immunology
D019409:Interleukin-15; D007376:Interleukin-2; D013745:Tetanus Toxoid