Anti-CD3 priming generates heterogeneous antigen-specific memory CD4 T cells.
Anti-CD3 activation of peripheral T cells is used in adoptive immunotherapy for cancer and HIV infection, but the long-term fate of anti-CD3-primed T cells in vivo is not known. In this study, we demonstrate that anti-CD3-mediated activation of influenza hemagglutinin (HA)-specific TCR-transgenic CD4 T cells results in generation of a long-lived HA-specific memory CD4 T cell population when transferred into lymphocyte-deficient and intact mouse hosts. This anti-CD3-primed memory population is indistinguishable from HA peptide-primed memory CD4 T cells in terms of phenotype, rapid recall function, and enhanced proliferative capacity. Moreover, anti-CD3 priming generates phenotypically heterogeneous memory subsets in lymphoid and non-lymphoid sites. Our results suggest that anti-CD3 has potential efficacy in generating memory responses in adoptive immunotherapies and vaccines and that the tissue distribution and maintenance of heterogeneous lymphoid and non-lymphoid memory T cell subsets are a stochastic process that can occur independent of antigen or TCR specificity.
Patke
Deepa S
DS
Division of Transplantation, Department of Surgery, University of Maryland School of Medicine, MSTF Building, Room 400, 685 W. Baltimore St., Baltimore, MD 21201, USA.
Ahmadzadeh
Mojgan
M
Bingaman
Adam W
AW
Farber
Donna L
DL
D000818:Animals; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009975:Orthomyxoviridae / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
D017252:CD3 Complex; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell