Thymic function and output of recent thymic emigrant T cells during intracranial glioma progression.
One of the hallmarks of patients with glioblastoma multiforme (GBM) is profound lymphopenia mostly confined to the T cell lineage. A deficiency in the production of naive T cells from the thymus could contribute to the lymphopenia seen in GBM patients. In this study we asked whether thymic function and the production of recent thymic emigrant (RTE) T cells from the thymus was influenced by intracranial (i.c.) glioma progression. We found significant thymic involution in animals with progressive i.c. gliomas. Involuted thymi from animals with progressive i.c. T9.F gliomas showed dramatic losses of CD4+ CD8+ (DP) thymocytes. Microscopic analysis complemented those findings by demonstrating a reversal of the typical cortico-medullary structure. Significant increases in apoptosis accompanied the rapid loss of viable thymocytes, which was prevented in part by adrenalectomy, suggesting a dominant role for endogenous glucocorticoids. This thymic involution was also associated with a significant decrease in peripheral RTE T cells, reflecting the diminished thymic function. Finally, we found that CD8+ RTE T cells were enriched in progressively growing T9 gliomas, which points to an immunological role for RTE's in anti-glioma immunity. Our findings may shed light on the significance of thymic function for anti-glioma immunity and the response to immunotherapeutic treatment paradigms.
Prins
Robert M
RM
Department of Anatomy and Surgery, Virginia Commonwealth University/Medical College of Virginia, Richmond, VA, USA.
Graf
Martin R
MR
Merchant
Randall E
RE
Black
Keith L
KL
Wheeler
Christopher J
CJ
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000473:pathology*; D013950:Thymus Gland / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors