tetano
Editor, Senior Moderator
Front Immunol. 2017 Sep 25;8:1156. doi: 10.3389/fimmu.2017.01156. eCollection 2017.
[h=1]CD30 Is Dispensable for T-Cell Responses to Influenza Virus and Lymphocytic Choriomeningitis Virus Clone 13 but Contributes to Age-Associated T-Cell Expansion in Mice.[/h] Zhou AC[SUP]1[/SUP], Snell LM[SUP]1[/SUP], Wortzman ME[SUP]1[/SUP], Watts TH[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] CD30 is a tumor necrosis factor receptor (TNFR) family member whose expression is associated with Hodgkin's disease, anaplastic large cell lymphomas, and other T and B lymphoproliferative disorders in humans. A limited number of studies have assessed the physiological role of CD30/CD30 ligand interactions in control of infection in mice. Here, we assess the role of CD30 in T-cell immunity to acute influenza and chronic lymphocytic choriomeningitis virus (LCMV) clone 13 infection, two viral infections in which other members of the TNFR superfamily are important for T-cell responses. We show that CD30 is expressed on activated but not resting CD4 and CD8 T cells in vitro, as well as on regulatory T cells and marginally on T helper 1 cells in vivo during influenza infection. Despite this, CD4 and CD8 T-cell expansion in response to influenza virus was comparable in CD30[SUP]+/+[/SUP] and CD30[SUP]-/-[/SUP] littermates, with no discernable role for the pathway in the outcome of influenza infection. Similarly, during persistent infection with LCMV clone 13, CD30 plays no obvious role in CD4 or CD8 T-cell responses, the level of T-cell exhaustion or viral control. In contrast, in the steady state, we observed increased numbers of total CD4 and CD8 T cells as well as increased numbers of regulatory T cells in unimmunized older (~8 months) CD30[SUP]+/+[/SUP] but not in CD30[SUP]-/-[/SUP] age-matched littermates. Naive T-cell numbers were unchanged in the aged CD30[SUP]+/+[/SUP] mice compared to their CD30[SUP]-/-[/SUP] littermate controls, rather the T-cell expansions were explained by an increase in CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] CD44[SUP]mid-hi[/SUP]CD62L[SUP]-[/SUP] effector memory cells, with a similar trend in the central memory T-cell compartment. In contrast, CD30 did not impact the numbers of T cells in young mice. These data suggest a role for CD30 in the homeostatic regulation of T cells during aging, contributing to memory T-cell expansions, which may have relevance for CD30 expression in human T-cell lymphoproliferative diseases.
[h=4]KEYWORDS:[/h] CD30; T cells; age-dependent T-cell expansion; influenza; lymphocytic choriomeningitis virus; viral
PMID: 28993768 PMCID: PMC5622170 DOI: 10.3389/fimmu.2017.01156
Free PMC Article
[h=1]CD30 Is Dispensable for T-Cell Responses to Influenza Virus and Lymphocytic Choriomeningitis Virus Clone 13 but Contributes to Age-Associated T-Cell Expansion in Mice.[/h] Zhou AC[SUP]1[/SUP], Snell LM[SUP]1[/SUP], Wortzman ME[SUP]1[/SUP], Watts TH[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] CD30 is a tumor necrosis factor receptor (TNFR) family member whose expression is associated with Hodgkin's disease, anaplastic large cell lymphomas, and other T and B lymphoproliferative disorders in humans. A limited number of studies have assessed the physiological role of CD30/CD30 ligand interactions in control of infection in mice. Here, we assess the role of CD30 in T-cell immunity to acute influenza and chronic lymphocytic choriomeningitis virus (LCMV) clone 13 infection, two viral infections in which other members of the TNFR superfamily are important for T-cell responses. We show that CD30 is expressed on activated but not resting CD4 and CD8 T cells in vitro, as well as on regulatory T cells and marginally on T helper 1 cells in vivo during influenza infection. Despite this, CD4 and CD8 T-cell expansion in response to influenza virus was comparable in CD30[SUP]+/+[/SUP] and CD30[SUP]-/-[/SUP] littermates, with no discernable role for the pathway in the outcome of influenza infection. Similarly, during persistent infection with LCMV clone 13, CD30 plays no obvious role in CD4 or CD8 T-cell responses, the level of T-cell exhaustion or viral control. In contrast, in the steady state, we observed increased numbers of total CD4 and CD8 T cells as well as increased numbers of regulatory T cells in unimmunized older (~8 months) CD30[SUP]+/+[/SUP] but not in CD30[SUP]-/-[/SUP] age-matched littermates. Naive T-cell numbers were unchanged in the aged CD30[SUP]+/+[/SUP] mice compared to their CD30[SUP]-/-[/SUP] littermate controls, rather the T-cell expansions were explained by an increase in CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] CD44[SUP]mid-hi[/SUP]CD62L[SUP]-[/SUP] effector memory cells, with a similar trend in the central memory T-cell compartment. In contrast, CD30 did not impact the numbers of T cells in young mice. These data suggest a role for CD30 in the homeostatic regulation of T cells during aging, contributing to memory T-cell expansions, which may have relevance for CD30 expression in human T-cell lymphoproliferative diseases.
[h=4]KEYWORDS:[/h] CD30; T cells; age-dependent T-cell expansion; influenza; lymphocytic choriomeningitis virus; viral
PMID: 28993768 PMCID: PMC5622170 DOI: 10.3389/fimmu.2017.01156
Free PMC Article