CD62L (L-selectin) down-regulation does not affect memory T cell distribution but failure to shed compromises anti-viral immunity.
The down-regulation of CD62L that accompanies T lymphocyte activation is thought to redirect cells away from lymph nodes to sites of infection. In this study, CD62L was maintained on Ag-activated T cells and their distribution, and ability to clear pathogen from peripheral sites determined. CD62L was down-regulated on Ag-specific CD8 T cells in lungs of C57BL/6 mice but maintained in CD62L transgenic mice at day 8 after influenza infection. However, the numbers of influenza-specific CD8 T cells recruited were similar in CD62L transgenic and C57BL/6 mice. Memory CD8 T cell numbers in the lungs and noninvolved organs 100 days after primary infection were similar in CD62L transgenic and C57BL/6 mice, despite differing CD62L expression. Transgenic mice expressing wild-type CD62L cleared a recombinant vaccinia virus expressing an influenza-derived CD8 T cell epitope as efficiently as C57BL/6 mice. However, transgenic mice expressing a protease resistant mutant of CD62L showed significantly delayed viral clearance, despite normal CTL generation and the presence of CD107a and IFN-gamma expressing influenza-specific CD8 T cells. These results demonstrate that CD62L down-regulation is not required for CD8 memory cells to home to sites of infection. However, their ability to clear virus is significantly compromised if CD62L shedding is abrogated.
Richards
Hannah
H
Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, UK.
Longhi
M Paula
MP
Wright
Kate
K
Gallimore
Awen
A
Ager
Ann
A
D000818:Animals; D015536:Down-Regulation; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007251:Influenza, Human / Q000276:immunology*; D019041:L-Selectin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010053:Ovary / Q000276:immunology; D010447:Peptide Hydrolases / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D018984:Epitopes, T-Lymphocyte; D052118:Lysosomal-Associated Membrane Protein 1; D019041:L-Selectin; D010447:Peptide Hydrolases