Effects of protein insufficiency on immune responsiveness

Abstract
Experiments over a 3-year period have shown that chronic, moderately severe, protein deprivation enhances cell-mediated immunity while either not affecting or depressing humoral immunity. This differential effect of protein insufficiency alone on the two major limbs of the immunological response was demonstrated in successive progeny of normally fed and protein-depleted mothers, using standardized fostering procedures. Isocaloric diets of 8 and 27% casein were used; all other nutrients except protein were kept constant. The differential effect of chronic protein insufficiency on immune responsiveness was demonstrated by the results of seven categories of experiments. Chronic protein insufficiency: 1) did not affect the primary humoral antibody response to Brucella abortus (humoral): 2) depressed the primary humoral antibody response to sheep erythrocytes (paired-feeding) (humoral); 3) enhanced the graft-versus-host reaction as measured by spleen indices using the Simonsen assay (paired-feeding) (cellular); 4) accelerated rejection of skin allografts in nonneonatally thymectomized mice versus both normally fed, nonthymectomized mice and neonatally thymectomized, protein-deficient animals (cellular); 5) enhanced the phytohemagglutinin-induced blastogenic effect on spleen cells (paired-feeding) (cellular); 6) enhanced phagocyte activity of peritoneal macrophages (paired-feeding) (cellular); 7) enhanced resistance to viral infection (pseudorabies) while depressing resistance to bacterial infection (streptococcus, type 6) (cellular). It is postulated that chronic protein insufficiency may lead to increased output of thymic hormone(s) (thymin). Chronic protein insufficiency may operate in several ways to enhance cell-mediated immunity, any of which may involve thymin overproduction. However, we believe that the two most likely mechanisms for this enhancement are: 1) an absolute increase in the T cell population and 2) increased immunocompetence of each effector T cell.