CD62L (L-Selectin) Down-Regulation Does Not Affect Memory T Cell Distribution but Failure to Shed Compromises Anti-Viral Immunity

Abstract

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-γ 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.

Mannosylated lipopetides as model vaccines for targeting the mannose receptor

“…Studies have shown that CD62L shedding plays an important role in T cell activation in the lymph nodes. Further, it is confirmed that although CD62L is present on memory T cells its shedding is not essential for the production of memory T cells or T cell immigration to the infection site, thus, the lack of shedding can affect the viral elimination effect [339].…”

“…It is also argued that this epitope also bears at least one B cell epitope (323)(324)(325)(326)(327)(328)(329)(330)(331)(332)(333)(334)(335)(336)(337)(338)(339), however, there is only one study that has mentioned the presence of the B cell epitope [327]. In a study by Sun et al, it was shown that 50% of the B cell response generated by the OVA protein was antibody specific to the OVA323-339 epitope [327].…”

“…In a study by Sun et al, it was shown that 50% of the B cell response generated by the OVA protein was antibody specific to the OVA323-339 epitope [327]. As the vaccine structures (G1-6) contain the CD4 epitope (OVA [323][324][325][326][327][328][329][330][331][332][333][334][335][336][337][338][339], the in vivo ability of vaccine structures (G1-9) for a T cell activation proliferation was assessed. Here, OT-II proliferating cells are considered to be activated when T cells expressing CD45.2 increase in percentage over the total parental CD4 + T cells [329].…”

“…In this study, the native OVA protein was administered to mice genetically modified to have the MR expressed on DCs and showed that the OVA protein could activate OVA-specific CD8 T cells (OVA257-264 sensitive T cells from transgenic mice, OT-I), but was not able to activate OVA-specific CD4 T cells (OVA323- 339 sensitive T cells from transgenic mice, OT-II). This highlights an important aspect of uptake through the MR that can affect antigen specific T cell response depending on the selection of antigens in a vaccine structure [6,193].…”

“…The OVA protein naturally exists as a glycoprotein, however, it was discovered that the OVA [323][324][325][326][327][328][329][330][331][332][333][334][335][336][337][338][339] and OVA 1-10 sequences of the OVA protein bore a B cell epitope that was capable of inducing a T cell response. This discovery was obtained by T cell mediated IgE responses that were observed against an assumed B cell epitope inside OVA323-339 and OVA1-10 peptides [185].…”