Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy.

Publication Title

J Immunother Cancer

Authors

Gail D Sckisel
Annie Mirsoian
Christine M Minnar
Marka R Crittenden, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, PortlandFollow
Brendan Curti, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland, ORFollow
Jane Q Chen
Bruce R Blazar
Alexander D Borowsky
Arta M Monjazeb
William J Murphy

Document Type

Article

Publication Date

1-1-2017

Keywords

Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Humans; Immunotherapy; Mice; Mice, Inbred BALB C; Phenotype; Spleen

Abstract

BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy.

METHODS: Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype.

RESULTS: Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to CD62L

CONCLUSIONS: These data highlight PD-1 expressing and/or T

TRIAL REGISTRATION: ClinicalTrials.gov NCT01416831. Registered August 12, 2011.

Area of Special Interest

Cancer

Specialty/Research Institute

Earle A. Chiles Research Institute

Specialty/Research Institute

Oncology