Analysis of adjuvant function by direct visualization of antigen presentation in vivo: Endotoxin promotes accumulation of antigen-bearing dendritic cells in the T cell areas of lymphoid tissue
Cre. Sousa et Rn. Germain, Analysis of adjuvant function by direct visualization of antigen presentation in vivo: Endotoxin promotes accumulation of antigen-bearing dendritic cells in the T cell areas of lymphoid tissue, J IMMUNOL, 162(11), 1999, pp. 6552-6561
T cell activation requires exposure to processed Ag and signaling by cytoki
nes and costimulatory ligands, Adjuvants are thought to enhance immunity pr
imarily through up-regulation of the latter signals, Here, we explore the e
ffect of the bacterial adjuvant, endotoxin, on Ag presentation by B cells a
nd dendritic cells (DC), Using an mAb (C4H3) specific for the hen egg lysoz
yme (HEL) 46-61 determinant bound to I-A(k), we analyze processed Ag expres
sion and the tissue distribution of presenting cells following systemic adm
inistration of soluble HEL to mice. In both LPS-responsive and -hyporespons
ive mice given endotoxin-containing HEL, B cells rapidly display surface 46
-61/I-A(k) complexes. In marked contrast, in LPS-hyporesponsive mice, splen
ic DC show little gain in C4H3 staining. In LPS-responsive animals, interdi
gitating DC in T cell areas show no staining above background at early time
s after HEL administration, but C4H3(+) DC rapidly accumulate in the outer
periarteriolar lymphoid sheaths (PALS) and in follicular areas. Within a fe
w hours, C4H3(+) DC appear in the T cell areas,concomitant with a decline i
n C4H3(+) cells in the outer PALS, suggesting migration between these two s
ites. Endotoxin enhancement of C4H3 staining is seen for both CD8 alpha(-)
and CD8 alpha(+) DC subsets. These data suggest that a major effect of adju
vants is to promote mobilization of Ag-bearing DC to the T areas of lymphoi
d tissue, and possibly also to enhance Ag processing by these DC. Thus; mic
robial products promote T cell immunity not only through DC activation for
cosignaling,,but through improvement in signal 1 delivery.