Defective antigen presentation in chronically protein-deprived mice.
Immunodeficiency syndromes associated with protein-energy malnutrition (PEM) have been documented extensively, although to date the mechanism underlying these defects remains uncharacterized. In this study, we have evaluated T, B, and antigen-presenting cell functions of malnourished mice fed a 4% protein diet compared with litter-mate controls fed a 20% protein diet. Spleen cells from malnourished mice presented both soluble foreign protein and allogeneic MHC antigens less efficiently than control mice. However, T cells from malnourished animals demonstrated effective or enhanced specific T-cell activation when stimulated with allogeneic cells, while B cells from protein-deprived animals responded normally in proliferative responses to T-cell driven cognate and non-cognate, as well as mitogen, stimulation. To assess further antigen-presenting cell function, three requirements for successful antigen presentation were evaluated. First, the proliferation of the IL-1-dependent cloned T-cell line D10 demonstrated a slight deficiency in IL-1 production by malnourished splenic antigen-presenting cells, and the addition of saturating amounts of IL-1 to the assay could partially reconstitute function. Second, quantitative cell-sorter analysis revealed minimal deficiencies of spleen-cell Ia expression. Third, antigen-processing function was assayed in vitro by using processed antigen fragments; no improvement in protein-deprived antigen-presenting function resulted. Together, these findings suggest that either decreased Ia glycoprotein expression on a critical subset of antigen-presenting cells (APCs) or a quantitative deficiency in such a subset of cells, or both, underlie the defective antigen-presenting cell function observed in chronic protein deprivation (CPD).
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology; D011502:Protein-Energy Malnutrition / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D010047:Ovalbumin