Lb. Adams et al., EFFECTS OF ESSENTIAL FATTY-ACID DEFICIENCY ON PROSTAGLANDIN E(2) PRODUCTION AND CELL-MEDIATED-IMMUNITY IN A MOUSE MODEL OF LEPROSY, Infection and immunity, 65(4), 1997, pp. 1152-1157
Results from animal and in vitro studies suggest that essential fatty
acid (EFA) deficiency enhances cell-mediated immunity by reducing prod
uction of prostaglandins with immunosuppressive actions, However, dire
ct experimental evidence that EFA deficiency enhances T-lymphocyte fun
ction in vivo has not been obtained, In this study, athymic (nu/nu) mi
ce were infected in the footpads with Mycobacterium leprae and fed a l
inoleic acid-free diet, These mice, and infected nu/nu mice on control
diets, were given an adoptive transfer of M, leprae-primed, T-cell-en
riched lymphocytes, After 2 weeks, M, leprae bacilli merr: harvested f
rom the recipient mice and bacterial viability was determined by the B
ACTEC system. M. leprae recovered from recipient mice fed control diet
s displayed Little reduction in metabolic activity. In contrast, M. le
prae from recipient mice fed the EFA deficient (EFAD) diet exhibited m
arkedly reduced viability. In vitro, donor cells from M. leprae-primed
mice secreted elevated levels of gamma interferon upon exposure lu th
e bacilli, These cells also exhibited an enhanced proliferative respon
se, which was reduced by exogenous prostaglandin E(2) (PGE(2)), In add
ition, M. leprac-infected granuloma macrophages (M phi) from EFAD reci
pient nu/nu mice secreted significantly less PGE(2) than granuloma M p
hi from mice on control diets, These data suggest that enhanced levels
of M phi-generated PGE(2), induced by M. leprae or its constituents,
could act as an endogenous negative modulator of the immune response o
ccurring in the microenvironment of the lepromatous granuloma.