Macrophage Ia expression in athymic nude versus neonatally thymectomized mice

The requirement of the thymus for the production of Ia-inducing lymphokine was studied in athymic nude, neonatally thymectomized (NTx), and sham-operated (Sham) mice. The peritoneal macrophages from NTx mice immunized with viable Listeria monocytogenes 14 days previously contained as high a proportion of Ia-bearing macrophages as those from Sham mice, while those from athymic nude mice contained only a small proportion. Intraperitoneal injection of a culture supernatant derived from immune spleen cells of NTx mice induced Ia-rich exudates in recipient normal mice just as well as did a corresponding supernatant from cells of Sham mice, but that from cells of athymic nude did not. The production of Ia-inducing lymphokine in culture supernatants of immune spleen cells from both NTx and Sham mice was abolished by pretreatment of cells with anti-Thy-1.2 antibody plus complement. These results suggest that a T cell subset responsible for the production of Ia-inducing lymphokine requires the presence of the thymus for just a short period in the ontogenic development.     

Polyoma virus infection in neonatally thymectomized hamsters

Summary Inoculation of polyoma virus into weanling hamsters, thymectomized as neonates, has resulted in the production of tumors. In contrast, the sham operated litter mates developed no demonstrable neoplasms over a 12–18 month period of observation. Thus, it has been confirmed in these studies that neonatal thymectomy may render some resistant animals susceptible to the effects of an oncogenic virus.When inoculated with high titers of polyoma virus, both the thymectomized and sham operated animals developed hemorrhagic lesions, primarily of the liver. The histology of these hemorrhagic lesions has revealed no neoplastic features.It is suggested that the hemorrhagic and neoplastic responses to polyoma virus infection in hamsters may representin vivo, respectively, lytic and proliferative cellular responses to the infection.Dedicated to ProfessorJohn F. Enders on the occasion of his 70th birthday.Supported in part by U.S. Public Health Service general research support grant FRO5486.     

Pathogenesis of K papovavirus infection in athymic nude mice

The fatal outcome of K virus infection in infant mice and cytoxan-treated adult mice is related to their inability to mount a prompt antibody response to the virus. Athymic nude mice infected with K virus exhibited no clinical illness and no detectable virus-specific immunoglobulin G (IgG) response, but they did exhibit a low level of virus-specific immunoglobulin M response. Transfer of spleen cells from K virus-primed nude mice to infected infant mice conferred complete protection against K virus-induced mortality. This protection was diminished by the depletion of B cells but not by the depletion of adherent cells from the primed spleen cells. B cell response is therefore important in the recovery of nude mice from K virus infection.     

Induction of experimental amyloidosis in neonatally thymectomized mice

Outbred Swiss albino mice thymectomized at birth show a marked lymphocyte depletion and a striking impairement of the capacity to form antibodies against sheep red blood cells (RBC) and to reject allogeneic skin grafts, as compared to sham-operated controls, but rarely exhibit symptoms of wasting disease. Neonatal ablation of the thymus neither significantly modifies the susceptibility of mice chronically exposed to casein to develop amyloidosis nor does it lessen the gravity of the disease, when compared to sham-operated controls.

These results are interpreted as evidence against an autoimmune pathogenesis of the casein-induced experimental amyloidosis. However, some reservations are imposed by recent data which hint at the possibility that thymectomy may sometimes favour, instead of repress, the development of autoimmune diseases in man and rodents.

     

Role of thymus for N-acetyl muramyl-L-alanyl-D-isoglutamine-induced polyarthritis and granuloma formation in euthymic and athymic nude rats or in neonatally thymectomized rats.

A synthetic adjuvant, N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP), produced extremely severe polyarthritis with almost 100% incidence in Rowett euthymic rnu/+ rats, but the same dose of MDP (100 microgram) did not produce the disease in athymic rnu/rnu rats. Five hundred micrograms of MDP or 0.2 mg of heat-killed Mycobacterium bovis BCG, however, produced mild and transient polyarthritis in nude rats with very low incidence. We have not yet succeeded in reconstituting the disease susceptibility of nude rats by using thymus cells from normal rnu/+ rats. After intradermal inoculation of 100 microgram of MDP, nude rats developed small granulomas with a little necrosis and very few multinucleated giant cells only in the regional lymph nodes, whereas, in addition to the development of polyarthritis, euthymic rnu/+ rats developed typical granuloma with massive necrosis accompanied by numerous polymorphonuclear leukocytes and sparse multinucleated giant cells in the regional lymph nodes. Thymus cell-reconstituted rnu/rnu rats developed granuloma with sparse giant cells, relatively large areas of necrosis, and many polymorphonuclear leukocytes. Neonatal thymectomy may depress adjuvant-induced arthritis in the high-responder Lewis rats and enhance the disease development in the low-responder F344 rats. These findings suggested that (i) thymus plays an important role in promoting the development of MDP-induced arthritis; (ii) MDP-induced granuloma formation does not require thymus functions; (iii) the thymus functions may however be involved in the development of massive necrosis surrounded by considerable polymorphonuclear leukocyte infiltration, the mechanisms of which remain to be determined; and (iv) there is no direct correlation between granuloma formation and development of adjuvant arthritis.     

Amyloidosis in neonatally thymectomized and anti-lymphocyte serum treated mice

A marked lymphocyte depletion and a striking impairment of their capacity to form antibodies against sheep erythrocytes was shown by outbred Swiss albino mice thymectomized or sham-thymectomized at birth and later treated with anti-lymphocyte serum.

Ninety-four per cent of allogeneic and 53% of heterogeneic skin grafts applied to the former, and 63% and 0% of those applied to the latter, survived up to the time of killing, i.e. 41 days after transplantation.

The remaining allogeneic and heterogeneic skin grafts were rejected by mice belonging to both experimental groups in a minimum of 18 days and a maximum of 35 days, which is much longer than is usually required by normal recipients (allogeneic grafts = about 10–11 days; heterogeneic grafts = about 7–8 days).

Despite the severe immunological depression caused by anti-lymphocyte serum treatment, either associated or not with neonaial thymectomy, all the mice chronically exposed to casein developed amyloidosis.

The present results are in accordance with previous findings indicating that mechanisms other than immunity may be involved in the pathogenesis of amyloidosis.

     

Experimental Q fever infection in congenitally athymic nude mice.

Congenitally athymic nude (nu/nu) mice and their phenotypically normal (nu/+) euthymic littermates were exposed to Coxiella burnetii administered as small-particle aerosols. After challenge, both strains of mice became infected, as characterized by rickettsemia, viable rickettsiae in the spleen, and serological conversion. The major difference noted was that euthymic animals had cleared rickettsiae from peripheral circulation and the spleen within 14 days. In contrast, rickettsiae were detected and isolated from spleen and blood of athymic mice through 60 days.     

Chronic chlamydial genital infection in congenitally athymic nude mice.

Congenitally athymic nude mice and their heterozygous counterparts were inoculated intravaginally with the chlamydial agent of mouse pneumonitis, a Chlamydia trachomatis biovar. Heterozygous mice resolved their infections in 20 days, whereas nude mice developed chronic infections which lasted at least 265 days and did not resolve within the time course of the experiments. Heterozygous mice produced high levels of antibody in both serum and secretions in contrast to nude mice, which produced very low levels of antibody in serum alone.     

Chronic infection with Trypanosoma musculi in congenitally athymic nude mice.

Trypanosoma musculi produces a chronic infection with a consistently elevated parasitemia in nude mice. Thymic reconstitution of nude mice restores immunity to the infection.     

Persistent Cryptosporidium infection in congenitally athymic (nude) mice.

Nude (nu/nu) BALB/c mice and their white (nu/+) littermates were experimentally infected with Cryptosporidium sp. at 6 days of age. In white mice, the infection was transient, but in nude mice a persistent infection developed that was characterized by diarrhea and, occasionally, death. There were villus atrophy and crypt hyperplasia in the small intestine of infected nude and white mice necropsied at 11 days of age. Persistently infected nude mice had, in addition to the above small intestinal lesions, diffuse cystic mucosal hyperplasia and crypt abscesses in the large intestine at 56 days of age. These results suggest that T cells are required for recovery from the Cryptosporidium infection but are not required for epithelial cell loss in cryptosporidiosis. Both nude and white mice appeared to be relatively more resistant to Cryptosporidium infection at 42 days of age than at 6 days of age.     

Generation of Listeria monocytogenes-specific T cells mediating delayed footpad reaction and protection in neonatally thymectomized mice but not in nude mice

Neonatally thymectomized (NTx) mice, sham-operated control mice and congenitally athymic nude mice were immunized with viable Listeria monocytogenes and their spleen cells examined for the capacity to transfer both delayed footbad reaction and protection against challenge at the site of local transfer. Cells from immune NTx mice conferred significant degrees of delayed footpad reaction and protection comparable to sham mice, while cells from immune nude (nu/nu) mice did not. This abilty was completely eliminated by the treatment of cells with anti-Thy1, anti-Lytl or anti-L3T4 antibody plus complement but not with anti-Lyt2 antibody plus complement. These results indicated that NTx mice can normally mount the immunity to L. monocytogenes by generating Lyt1⁺2^–, L3T4⁺ T cells. Immune competence of NTx mice and thymus dependency of various immune responses are discussed.     

Alpha-fetoprotein and phagocytosis in athymic nude mice

Alpha-fetoprotein (AFP) was found to suppress the phagocytic activity of the blood monocytes and neutrophils in vitro. The amounts of AFP detectable by immunofluorescence in the livers of nu/nu, nu/+ and +/+ mice were quite comparable, and thus could not have been responsible for the alterations in phagocytosis found in leukocytes of athymic nude mice during their ontogenetic development.