Effect of molecular size on the ability of zwitterionic polysaccharides to stimulate cellular immunity.
The large-molecular-sized zwitterionic capsular polysaccharide of the anaerobe Bacteroides fragilis NCTC 9343, designated polysaccharide (PS) A, stimulates T cell proliferation in vitro and induces T cell-dependent protection against abscess formation in vivo. In the present study, we utilized a modification of a recently developed ozonolytic method for depolymerizing polysaccharides to examine the influence of the molecular size of PS A on cell-mediated immunity. Ozonolysis successfully depolymerized PS A into structurally intact fragments. PS A with average molecular sizes of 129.0 (native), 77.8, 46.9, and 17.1 kDa stimulated CD4+-cell proliferation in vitro to the same degree, whereas the 5.0-kDa fragment was much less stimulatory than the control 129.0-kDa PS A. Rats treated with 129.0-kDa, 46.9-kDa, and 17.1-kDa PS A molecules, but not those treated with the 5.0-kDa molecule, were protected against intraabdominal abscesses induced by challenge with viable B. fragilis. These results demonstrate that a zwitterionic polysaccharide as small as 22 repeating units (88 monosaccharides) elicits a T cell-dependent immune response. These findings clearly distinguish zwitterionic T cell-dependent polysaccharides from T cell-independent polysaccharides and give evidence of the existence of a novel mechanism for a polysaccharide-induced immune response.
Kalka-Moll
W M
WM
Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Division of Infectious Disease, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Tzianabos
A O
AO
Wang
Y
Y
Carey
V J
VJ
Finberg
R W
RW
Onderdonk
A B
AB
Kasper
D L
DL
D018784:Abdominal Abscess / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D001442:Bacteroides Infections / Q000276:immunology / Q000517:prevention & control; D001441:Bacteroides fragilis / Q000276:immunology; D002021:Buffers; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007477:Ions; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002021:Buffers; D007477:Ions; D011135:Polysaccharides, Bacterial