Microglia phagocytose alloreactive CTL-damaged 9L gliosarcoma cells.
Intracranial adoptive transfers of alloreactive cytotoxic T lymphocytes (aCTL) for brain tumor treatment were safe and showed promise in preclinical and early clinical trials. To better understand the endogenous immune responses that may ensue following cellular therapy with aCTL, we examined the ability of microglia to phagocytose aCTL-damaged and undamaged rat 9L gliosarcoma cells in vitro and in vivo. In vitro, 5.5+/-0.9% of microglial cells isolated from adult tumor-bearing rat brains phagocytosed aCTL-damaged 9L cells, whereas microglia did not bind to or ingest undamaged 9L cells. Addition of supernates from either 9L cell cultures or from aCTL+9L co-incubate cell cultures to microglia did not significantly alter their ability to bind to or phagocytose damaged glioma cells even though the latter contained T helper 1 and 2 cytokines. At 3 days following intracranial 9L cell infusion, 17.5+/-0.1% of the microglia phagocytosed CFSE-labeled aCTL-damaged 9L tumor cells within the adult rat brain, confirming the in vitro data. The results suggest that microglia within the tumor microenvironment of the adult rat glioma model selectively remove damaged, but not undamaged, glioma cells.
Kulprathipanja
Nisha V
NV
Department of Immunology, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, B216, Denver, CO 80262, USA.
Kruse
Carol A
CA
D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5 / Q000378:metabolism; D001921:Brain / Q000166:cytology; D001932:Brain Neoplasms / Q000473:pathology* / Q000628:therapy; D039481:CD11b Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D005434:Flow Cytometry / Q000379:methods; D018316:Gliosarcoma / Q000473:pathology* / Q000628:therapy; D016219:Immunotherapy, Adoptive; D017628:Microglia / Q000473:pathology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010587:Phagocytosis / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology*; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects
D017304:Annexin A5; D039481:CD11b Antigen; D019384:Nucleic Acid Synthesis Inhibitors; D015638:Cytochalasin D