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T T MacDonald

Publications and source records attributed to T T MacDonald.

At least 181 records · Page 10Linked to original sources
PubMed1983

Immunosuppression caused by antigen feeding II. Suppressor T cells mask Peyer's patch B cell priming to orally administered antigen.

Peyer's patch (PP) cells transferred into sublethally irradiated recipients generated substantial IgM, IgG and IgA anti-sheep red blood cell (SRBC) plaque-forming cell (PFC) responses in the recipient spleen. If donor mice were given SRBC orally for 4-5 weeks prior to transfer, the adoptively transferred PP IgG and IgA responses were considerably suppressed, although the IgM responses were often unaffected. Co-injection of PP cells from antigen-fed mice with PP cells from normal mice resulted in marked suppression of the normal PP IgG and IgA response. However, treatment of PP cells from antigen-fed mice with anti-Thy-1.2 plus complement prior to cotransfer completely abrogated suppression of the IgG PFC response and partially abrogated the suppressed IgA response. B cells from the PP of antigen-fed mice, when transferred into SRBC-primed irradiated recipients (to provide T cell help) generated 2-3 times more IgG and IgA PFC than comparable numbers of B cells from the PP of normal mice. Thus antigen feeding generates suppressor T cells in PP which can mask the expression of B cell priming to orally administered antigen.

Administration, Oral↗
PubMed1982

Immunosuppression caused by antigen feeding. I. Evidence for the activation of a feedback suppressor pathway in the spleens of antigen-fed mice.

Sheep red blood cells (SRBC) administered by the oral route to normal mice elicited no detectable splenic anti-SRBC plaque-forming cell (PFC) response until 8 weeks of antigen feeding. At this time a splenic IgA anti-SRBC PFC response was detected. On the other hand, spleen cells taken from mice given oral SRBC for 1-5 weeks showed striking changes in their in vitro anti-SRBC responsiveness as compared to spleen cells from normal mice. This was evidenced by enhanced early (days 3-4) in vitro responses, followed by suppressed late (day 5-6) in vitro responses. Both early enhancement and late suppression were T cell-mediated. Early enhancement appeared to be mediated by helper T cells of the Lyt-1+2.3- phenotype. Late suppression was also mediated by Lyt-1+2.3- cells, but Lyt-2-bearing cells had to be present in culture for suppression to occur. Lyt-2-bearing cells could be replaced with normal T cells. Furthermore, elimination of cells bearing I-J-encoded determinants from the T cell population isolated from the spleens of antigen-fed mice also partially relieved suppression. Thus, antigen feeding appears to activate a feedback suppressor pathway in which Lyt-1+2.3-, I-J subregion determinant-bearing T cells can suppress immune responses by causing normal T cells to become suppressor effectors. No evidence was found to show that antigen feeding induced Lyt-1-2.3+ suppressor cells in the spleen, nor were any serum suppressor factors detected.

Animals↗
PubMed1982

Nonspecific resistance to infection expressed within the Peyer's patches of the small intestine.

Intraperitoneal or intraduodenal pretreatment of mice with dead Corynebacterium parvum failed to produce significant nonspecific resistance to Salmonella enteritidis infection in the Peyer's patches of the small intestine. However, mice pretreated with a single oral infection of live Listeria monocytogenes were capable of restricting the growth of S. enteritidis in the Peyer's patches. The ability of L. monocytogenes to induce nonspecific resistance was associated with the ability of this organism to cause an increase in the number of macrophages in the Peyer's patches.

Animals↗
PubMed1982

Enhancement and suppression of the Peyer's patch immune response by systemic priming.

Mice were immunized by a single injection of sheep red blood cells (SRBC) in Freund's complete adjuvant (FCA), and their Peyer's patch (PP) immune response was studied by in vitro culture, or transfer of PP cells into irradiated recipients. After both intra-peritoneal (i.p.) or sub-cutaneous (s.c.) immunization, PP cells showed greatly enhanced in vitro IgM plaque forming cell (PFC) responses to SRBC. The in vitro enhanced response was antigen-specific and was apparent up to 11 weeks post-immunization. It was also shown that PP from primed mice contained nylon wool non-adherent cells (N/A) which could enhance normal PP PFC responses in vitro. Peyer's patch cells from i.p. immunized mice transferred into irradiated recipients generated greatly enhanced splenic IgG and IgA anti-SRBC responses when compared to the response generated by normal PP cells. In contrast, PP cells taken from mice immunized s.c. showed suppressed IgG and IgA responses in irradiated recipients. Furthermore, whereas N/A cells from the PP of i.p. immunized mice greatly enhanced the response of normal PP cells in the irradiated recipients, N/A cells from the PP of s.c. immunized mice noticeably suppressed this response. These data show that systemic immunization can markedly alter PP immune function, and that these effects are probably T cell mediated.

Animals↗
PubMed1982

Isolation and functional characteristics of adherent phagocytic cells from mouse Peyer's patches.

Attempts were made to isolate adherent phagocytic cells (macrophages) from mouse Peyer's patch cell suspensions. Cell suspensions prepared by teasing apart the Peyer's patches contained no adherent phagocytic cells. However, if Peyer's patch fragments were treated with collagenase to disrupt the tissue matrix, cells prepared in this way contained a subpopulation of adherent phagocytic cells. These cells comprised only 0.1-0.2% of the total nucleated cell population of the Peyer's patch. Similar cells could also be isolated from the Peyer's patches of germ-free mice, but as judged by their ability to ingest opsonized erythrocytes, these cells were less activated than cells from the Peyer's patches of normal mice. Adherent cells from the Peyer's patches of normal mice could present antigen (ovalbumin) to T cells, and Peyer's patches cell suspensions containing adherent cells could be stimulated in vitro to produce an anti-sheep red blood cell plaque-forming cell response in the absence of 2-mercaptoethanol. These studies show that although the frequency of phagocytic adherent cells is extremely low in Peyer's patches, these cells have functions consistent with that of adherent cells in other lymphoid tissues.

Animals↗
PubMed1981

A functional relationship between delayed hypersensitivity and antibacterial immunity.

The injection of living Listeria Monocytogenes into the site of a delayed hypersensitivity reaction in the footpads of mice resulted in inactivation of the organism. No such inactivation occurred when L. monocytogenes was injected into normal footpads. A correlation was observed between the magnitude of the delayed hypersensitivity reaction and the level of antibacterial resistance expressed within the delayed hypersensitivity site.

Animals↗
PubMed1980

Cell-mediated immunity to intestinal infection.

Specified pathogen-free B6D2F1 mice were orally infected with various doses of Listeria monocytogenes. Oral inocula containing more than 2.5 X 10(8) live organisms consistently initiated infection in the Peyer's patches (PP) of the small intestine. At lower doses the infection was sporadic, with many mice showing no apparent infection in the PP. The PP appeared to be the only site of tissue invasion and L. monocytogenes survival in the intestinal tissues, as no organisms were recovered from mucosa dissected free of all visible PP. Within the PP, the bacteria multiplied and the infection then disseminated to the mesenteric lymph node (MLN), liver, and spleen. However, bacteria were almost completely eliminated from all tissues, both systemic and gut-associated by 6 days postinfection. Mice given a primary L. monocytogenes infection by the oral route were highly resistant to subsequent intravenous or oral challenge. Likewise, sublethal intravenous infection rendered mice highly resistant to subsequent oral infection. In addition, lymphocytes from the PP, MLN, and spleens of mice recovering from a primary oral infection were able to adoptively transfer immunity to normal recipients. Finally, after oral infection, mice did not display peripheral delayed hypersensitivity to L. monocytogenes antigens until the organisms had penetrated to the spleen.

Administration, Oral↗
PubMed1980

Increased mucosal damage during parasite infection in mice fed an elemental diet.

We have examined the effects of parasite infection on the mucosal architecture of mice maintained on an elemental diet (Vivonex). Techniques used were conventional histology, micro-dissection and measurement of individual villi and crypts, and measurement of crypt cell proliferation rate by a metaphase accumulation technique. In normal, non-parasitised mice the elemental diet caused no change in villus height, crypt depth, or crypt cell proliferation. Likewise, the only effects of chronic protozoal infection or Nippostrongylus brasiliensis infection on the intestine of mice fed a normal diet have been a slight crypt hypertrophy and an increase in crypt cell proliferation rate without villous atrophy. However, the combination of elemental diet and parasite infection resulted in increased mucosal damage when compared with infected mice on a normal diet. Elemental diet mice infected with the nematode Nippostrongylus brasiliensis had significantly reduced villus height and correspondingly raised crypt length and metaphase accumulation rate. Elemental diet mice infected with the protozoan Giardia muris did not have villous atrophy but there was a significant increase in crypt length and metaphase accumulation when compared with infected normal diet mice. These experiments show that in two animal models of enteric infection, elemental diet has altered the host parasite relationship to the detriment of the host.

Animals↗
PubMed1979

Requirement for a bacterial flora before mice generate cells capable of mediating the delayed hypersensitivity reaction to sheep red blood cells.

A delayed-type hypersensitivity (DTH) reaction can be elicited by an injection of 10(8) sheep red blood cells (SRBC) into a rear footpad of conventional (CV) mice previously immunized with small doses of SRBC. In contrast, immunization of germ-free (GF) mice with the same doses of SRBC produced no DTH when immunization was by the intravenous (i.v.) route, and only weak reactions when immunization was by the subcutaneous (footpad) route. Varying the immunizing dose of SRBC, or the time at which DTH was elicited, did not produce a state of DTH responsiveness in i.v. immunized GF mice. However, the transfer of lymphocytes from CV mice, immunized 4 to 5 days previously with SRBC, into GF mice, conferred on GF mice the capacity to express DTH. Although DTH was not readily demonstrable in GF mice immunized with SRBC, they nevertheless produced normal levels of hemagglutinating antibody to SRBC. Finally, it was shown that GF mice could generate a normal DTH response to SRBC if they were first monoassociated with a Gram-negative bacterial flora.

Animals↗
PubMed1979

Host responses to infection with Yersinia enterocolitica.

The mechanism of protective systemic immunity to Y. enterocolitica infection in mice was studied. It was determined that active immunization of mice with heat-killed yersiniae would induce a protective immune response against an intravenous challenge. This protective response was proven to be humoral in nature when it was demonstrated that passively transferred serum, but not cells, protected normal recipients against a lethal challenge. It was also shown that the immune serum caused opsonization of the microorganisms resulting in enhanced phagocytosis and killing of yersiniae by reticuloendothelial organs.

Animals↗
PubMed1978

Mouse Peyer's patches contain T cells capable of inducing the graft-versus-host reaction (GVHR).

The potential of cells from the Peyer's patches (PP) of normal adult DBA/2 Tru mice (DBA/2) to induce a graft-versus-host reaction when injected into (C57BL/6 Tru x DBA/2 Tru)F1 hybrid (B6D2F1) mice was studied. The injection of 10(6) to 10(7) DBA/2 PP or spleen cells i.p. into neonatal F1 mice produced a striking splenomegaly. Comparable doses of parental PP or spleen cells injected into a rear footpad of adult F1 mice also induced a marked enlargement of the draining popliteal lymph node. In addition, PP cells were also capable of producing a lethal runting syndrome when injected i.v. into sublethally irradiated adult F1 recipients. In all assays, injection of syngeneic B6D2F1 cells had little or no effect. Treatment of the DBA/2 PP cells with anti-theta serum and complement abolished their capacity to induce splenomegaly in neonatal F1 mice. The graft-versus-host reaction activity of the PP cells could also be eliminated by thymus deprivation of the donor DBA/2 mice. These data are contradictory to previous findings in which it was observed that mouse PP cells were unable to induce graft-versus-host reaction.

Animals↗
PubMed1978

Hypersensitivity reactions in the small intestine. IV. Influence of allograft rejection on small intestinal mucosal architecture: a scanning and transmission electron microscope study.

The effect of a local delayed hypersensitivity reaction (allograft rejection) on small intestinal architecture has been examined by using scanning electron microscopy of the mucosal surface. In isografts, regarded as a morphological basis for normality of the system, the villi appeared normal and finger like. In allografts the appearances ranged from fairly normal areas to others with stunted and ridged villi, and flat areas in which crypt mouths opened on to the flat mucosal surface. The fine structure of epithelial cells was studied further by transmission electron microscopy. There was an apparent reduction in the size of the microvillous border in allografts but no other consistent abnormality. The similarities between this model of allograft rejection, and untreated coeliac disease in man, are highlighted and contrasted with the effects of acute radiation injury on the intestine.

Animals↗
PubMed1978

Small intestinal epithelial cell kinetics and protozoal infection in mice.

The effects of chronic protozoal infection on small intestinal architecture have been examined in mice, infected with Giardia muris and Hexamita muris. Techniques used were conventional histology, quantitation of intraepithelial lymphocytes, microdissection and measurement of individual villi and crypts, and epithelial cell kinetic studies. The histology of small intestine from infected mice appeared normal apart from the intraepithelial lymphocyte numbers. Mean intraepithelial lymphocyte counts in two groups of uninfected mice were 11.6 and 13.6 per 100 epithelial cells, and in two groups of infected mice were 17.6 and 21.8. Dynamic studies showed that protozoal infection doubled the cell production per crypt per hour from mean values of 6.2, 7.3, and 8.2 in three groups of uninfected animals, to 11.8, 13.4, and 17.1 in groups of chronically infected mice. Cell production per villus was also influenced by protozoal infection, with values of 93, 99, and 101 cells per hr in groups of uninfected animals whereas in infected mice the values were 155, 162, and 180 cells per hr. Although there was no reduction in villus height in the infected animals, radioautography using [3H]thymidine confirmed that the enterocytes moved rapidly up the sides of the villi than was the case for uninfected mice.

Animals↗
PubMed1977

Technique for microdissection and measurement in biopsies of human small intestine.

A microdissection and measurement technique has been adapted for biopsy of human small intestine. Specimens fixed in alcohol and acetic acid are Schiff stained in bulk. Villi and crypts are then dissected out under a dissecting microscope, placed under a coverslip, examined, measured, and the number of mitoses in individual crypts counted. With this method specimens of normal small intestine have been found to have villi 500 microns to 1100 microns long and crypts 150 microns to 300 microns. These values were double those obtained when measuring sections of the same specimens stained with haematoxylin and eosin. The mean number of mitoses per crypt in normal duodenum and jejunum ranged from 1 to 12 and most of the cells in mitosis were in prophase or telophase. This rapid, sensitive, and inexpensive technique complements the available methods of measuring small intestinal architecture.

Biopsy↗