Differentiated regulation of allo-antigen presentation by different types of murine microglial cell lines.
We established granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent murine microglial clones and investigated the immune properties of four individual clones. All four clones expressed MHC class I and CD54 (ICAM-1) at similar levels. The 5-2, Ra2, and 6-3 clones expressed CD80 (B7-1), CD86 (B7-2), and MHC class II at low, medium, and high levels, respectively. Only the 6-3 clone expressed CD40. Generally, the levels of co-stimulation and CD 40 signals had a profound effect on the response to antigens. The 5-2, Ra2, and 6-3 clones, however, stimulated allogenic T-cell proliferation to the same extent or less compared to spleen cells. Although the 6-1 clone expressed co-stimulatory and MHC molecules at levels similar to Ra2, it suppressed allogenic T-cell proliferation, unlike Ra2. Thus, allo-antigen presentation by microglial clones was not correlated with the expression of CD40 and co-stimulatory molecules. When microglial clones were fixed with paraformaldehyde, they enhanced IL-2-dependent T-cell proliferation according to the level of their expression of co-stimulatory molecules. Furthermore, conditioned medium from the 6-1 clone inhibited the T-cell response to allo-antigen. This indicates that some factor(s) derived from a microglial subtype may play an important role in the regulation of T-cell proliferation in addition to the molecules involved in antigen presentation. Moreover, these results also suggest that there may be specialized subtypes of microglia that regulate the immune response in the CNS.
Kanzawa
T
T
Department of Neurosurgery, Niigata Brain Research Institute, Niigata University, Niigata, Japan. microgli@bri.niigata-u.ac.jp
Sawada
M
M
Kato
K
K
Yamamoto
K
K
Mori
H
H
Tanaka
R
R
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005434:Flow Cytometry; D005557:Formaldehyde / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D011108:Polymers / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D017077:Culture Media, Conditioned; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D007519:Isoantigens; D011108:Polymers; D005557:Formaldehyde; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C003043:paraform