S. Grabbe et al., DEFICIENT ANTIGEN PRESENTATION BY LANGERHANS CELLS FROM ATHYMIC (NU NU) MICE - RESTORATION WITH THYMIC TRANSPLANTATION OR ADMINISTRATION OFCYTOKINES/, The Journal of immunology, 151(7), 1993, pp. 3430-3439
Epidermal Langerhans cells (LC) are a unique subtype of I-A+ dendritic
cells able to present Ag for CD4-dependent immune responses. To inves
tigate whether cutaneous Ag presentation is regulated by thymic elemen
ts or soluble factors produced by thymus-derived cells, we compared LC
function in athymic nude mice and euthymic normal controls. Examinati
on of the ability of LC to present alloantigens to T cell-enriched res
ponder populations, and insulin to an insulin-specific T cell hybridom
a, demonstrated that this function is deficient in LC from inbred and
outbred strains of congenitally athymic (nu/nu) mice compared with eut
hymic litter mates. Adoptive transfer of thymic tissue from euthymic t
o athymic mice reconstituted the ability of LC derived from athymic mi
ce to present alloantigens. To investigate whether an altered local cy
tokine microenvironment was responsible for the diminished LC function
in athymic mice, various cytokines were administered in vivo and in v
itro before determination of alloantigen presentation by epidermal cel
ls from athymic and euthymic mice. Continuous intraperitoneal infusion
of granulocyte-macrophage colony stimulating factor (GM-CSF) or TNF-a
lpha, but not IL-1alpha or IL-2, restored alloantigen presenting abili
ty in athymic LC. In vitro preincubation of LC in GM-CSF or TNF-alpha
but not in other cytokines tested also reconstituted alloantigen prese
ntation by LC from athymic mice in most, but not all, of the experimen
ts performed. Furthermore, analysis of cytokine production by epiderma
l cells in athymic and euthymic mice revealed that epidermal cells fro
m athymic mice produce less GM-CSF and more TNF-alpha, but normal amou
nts of various other cytokines. However, reconstitution of athymic mic
e with thymic tissue did not result in normalization of GM-CSF or TNF-
alpha production by epidermal cells. These data suggest that LC Ag pre
senting ability is regulated by thymic factors and that adequate funct
ion of cutaneous APC in situ may require the continuous presence of su
fficient amounts of cytokines including GM-CSF and TNF-alpha.