Peptide immunization excludes antigen-specific T cells from splenic lymphoid compartments.
Using adoptive transfer of TCR-transgenic T cells, we examined the homing of transgenic T cells to splenic compartments in situ. After systemic immunization with peptide or protein antigen, the location of clonotypic T cells, cytokine production, cell surface markers, and apoptosis were assessed. There were distinct differences in the splenic homing of CD4(+) TCR-transgenic T cells in mice immunized with peptide as compared to mice immunized with whole-protein antigen. T cells in peptide-immunized mice were found almost exclusively in the splenic red pulp, but not in the T and B cell zones (white pulp), while the majority of T cells immunized with whole protein were found in the white pulp. Many more Fas ligand-expressing and apoptotic cells were present after peptide immunization than after whole-protein immunization. Localization of IL-4-, IL-2- and IFN-gamma-producing cells to the lymphocyte-containing splenic white pulp was only observed with whole-protein immunization. The unique homing and increased apoptosis of immune cells post peptide immunization may help explain the ineffectiveness of many peptide vaccines. Linkage of the same peptide epitope to a carrier protein increased white pulp T cell localization and decreased apoptosis, suggesting a strategy to enhance peptide vaccine responses.
Zhang
Lei
L
Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, USA.
Lizzio
Elaine F
EF
Chen
Trina
T
Kozlowski
Steven
S
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D023201:CD40 Ligand / Q000096:biosynthesis / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D053222:Fas Ligand Protein; D007114:Immunization / Q000379:methods*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D002352:Carrier Proteins; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; C111390:OVA 323-339; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D023201:CD40 Ligand; D010047:Ovalbumin