Impairment and Restoration of the Delayed Type Hypersensitivity in Germ‐Free Mice

Abstract

It was reported previously [8] that germfree (GF) mice infected with virulent bovine type tubercle bacilli showed more extensive and progressive infections than conventional mice; marked differences between GF and conventional mice were observed only in later stages of the infections. The lesions in GF mice were characterized by infiltration with many histiocytic cells engorging acid fast bacilli. These facts seemed to implicate an impaired immunological response following the infection in GF mice. It has been reported by Lerner [2] and Lev and Battisto [3] that GF guinea pigs showed a suppressed delayed type hypersensitivity. In the present experiments, we found an impaired delayed type footpad reaction to purified protein derivative (PPD) in GF mice infected or sensitized with the tubercle bacilli, and attempts were also made to restore the reactivity by association with enteric bacteria.

Impaired chemotactic responsiveness of macrophages from gnotobiotic rats

“…Lev and Battisto (15) reported that lymphoid cells from specifically immunized guinea pigs can transfer tuberculin sensitivity to CONV recipients but not to guinea pigs that have been reared in a GF environment. Similar observations have been made in mice (32). Preliminary experiments performed in rats (Jungi and McGregor, unpublished data) indicate that labeled lymphoblasts from the thoracic duct lymph of Listeria-infected CONV donors can move in substantial numbers from the blood into Listeria-induced exudates borne by GF rats.…”

“…been implicated in the expression of DTH (11), and since DTH reactions are impaired in GF subjects (14,15,32,33), it was of interest to compare the generation of MCA in GF and CONV subjects. To this end, six GF Fischer and a group of CONV Lewis x DA F1 hybrid rats were immunized in the forepaws with living L. monocytogenes.…”

“…However that may be, it has long been known that monocyte-derived macrophages have an indispensable role in the expression of DTH and cellular resistance to infection (16). Therefore it is logical to postulate that the diminished responsiveness of GB macrophages to chemotactic stimuli is causally related to the inability of flora-deprived animals to express DTH (14,15,32,33) and their susceptibility to tuberculosis (31). There is evidence to support this proposition.…”

“…Germ-free (GF) animals have a low level of resistance to the tubercle bacillus and to other infectious agents that provoke a vigorous cellmediated immune response in conventional (CONV) subjects (31). It also has been reported that GF guinea pigs (14,15) and GF mice (32,33) either fail to express delayed-type hypersensitivity (DTH) or show only feeble reactions to antigens that elicit florid responses in CONV animals. Unresponsiveness cannot be ascribed to a general failure of T-cell function, because GF anirnals can produce circulating antibodies to thymus-dependent antigens (5,29), and their capacity to reject allografts is unimpaired (25).…”

Immunity to Candida albicans.

“…Lymphoid organs in these animals are consid-erably smaller and contain very few mature lymphocytes (11, 151, 209). Lev and Battisto (122) have reported that germfree guinea pigs have impaired delayed-type hypersensitivity responses, and this has been confirmed by others (212,214). Jungi and McGregor (94) reported that macrophages in gnotobiotic rats had an impaired capacity for chemotaxis, but neutrophil chemotaxis, serum levels of chemotactic activity, and the capacity of lymphocytes to generate macrophage chemotactic factor were all normal.…”