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J F Miller

Publications and source records attributed to J F Miller.

At least 343 records · Page 19Linked to original sources

Cell-to-cell interaction in the immune response. X. T-cell-dependent suppression in tolerant mice.

Specific immunological tolerance was induced in CBA mice by a single injection of deaggregated fowl immunoglobulin G (FgammaG). The unresponsive state was stable on adoptive transfer and irreversible by pretreatment of tolerant cells with trypsin. Tolerant spleen cells could suppress the response of normal syngeneic recipients. They also suppressed the adoptive primary response of spleen cells to FgammaG in irradiated hosts. The inhibitory effect was on the indirect (7S) plaque-forming cell (PFC) response. Incubation of the tolerant cell population with anti-theta serum and complement reversed the suppressor effect. Furthermore, the addition of purified T cells from normal donors restored the capacity of the anti-theta serum-treated tolerant cells to transfer an adoptive response to FgammaG. The existence of FgammaG-reactive B cells was supported by the demonstration of normal numbers of antigen-binding cells in the spleen and thoracic duct lymph from tolerant animals. Moreover, the formation of caps by these cells implied that they could bind antigen normally. These experiments provided direct evidence for the existence of suppressor T cells in the tolerant population. Further evidence was derived from examination of the effect of antigen "suicide". Tolerant spleen cells were treated with radioactive FgammaG under conditions known to abrogate T-cell helper function. When these cells were transferred together with normal spleen cells into irradiated hosts, suppression of the primary adoptive response to FgammaG was no longer observed. Inhibition of an adoptive secondary response to FgammaG was obtained by transferring tolerant spleen cells with primed B cells provided high doses of tolerant cells were used. By contrast low doses exerted a helper rather than a suppressor effect in this system.

Animals↗

Effect of recent antigen priming on adoptive immune responses. II. Specific unresponsiveness of circulating lymphocytes from mice primed with heterologous erythrocytes.

When thoracic duct lymphocytes (TDL) or mesenteric lymph node (MLN) cells from mice primed 1 day before with either sheep erythrocytes (SRC) or horse erythrocytes (HRC) were transferred together with both SRC and HRC to irradiated mice, antibody responses measured 7 days later could not be detected to the priming antigen but were high to the other antigen. Furthermore, this unresponsiveness of TDL and MLN to the priming antigen could not be abrogated by delaying antigen challenge of the transferred cells for 1-2 wk. Previous work had shown that short-term priming with antigen also induced specific unresponsiveness in spleen cells on adoptive transfer. Unresponsiveness in these cells, however, was only of temporary duration, full recovery in the reactivity of the cells being observed when challenge with the priming antigen on transfer was delayed for 5 or more days. Since the present work showed that such recovery from initial unresponsiveness on transfer was unique to spleen cells and did not apply to TDL or MLN, it appeared that different mechanisms were responsible for the unresponsiveness in the three populations. It is proposed that the unresponsiveness detected in TDL and MLN cells in the present study resulted from a deficiency of antigen-reactive cells, these cells having been recruited to the spleen, i.e., a region of antigen concentration. This concept of antigen-induced selective recruitment of circulating lymphocytes was supported by evidence that (51)Cr-labeled heterologous erythrocytes indeed localized largely in the spleen after intravenous injection but not in MLN.

Animals↗

Induction of a primary antihapten response in vivo by a graft-vs.-host reaction.

A primary anti-NIP PFC response can be elicited by a GVH reaction provided certain structural requirements of the NIP-carrier are met. NIP-coated F(1) erythrocytes and NIP-coated parental erythrocytes give rise to substantial anti-NIP PFC responses in F(1) mice after the injection of parental spleens. These conjugates do not of themselves give rise to an anti-NIP PFC response and, in fact, normally give rise to NIP-specific tolerance. In contrast the GVH reaction is not able to enhance the primary anti-NIP PFC response to immunogenic NIP-conjugates.

Animals↗

Effect of recent antigen priming on adoptive immune responses. I. Specific unresponsiveness of cells from lymphoid organs of mice primed with heterologous erythrocytes.

When spleen, mesenteric lymph node, or Peyer's patch cells from mice primed 24 h before with either sheep erythrocytes (SRC) or horse erythrocytes (HRC) were transferred together with both SRC and HRC to irradiated mice, antibody responses measured 7 days later were very low to the priming antigen but high to the other antigen. This was demonstrated either by measuring numbers of antibody-forming cells in spleen or levels of hemagglutinins in serum. Specific unresponsiveness of the transferred cells was evident in both the 19S and 7S responses. It was observed only when strict experimental conditions were followed: (a) the cell donors had to be primed with not less than 10(9) erythrocytes given intravenously; (b) the cells had to be transferred between 1 and 2 days after antigen priming; (c) antibody responses in the recipients were measured within 7 days of cell transfer, i.e., partial recovery was evident by 11 days; (d) the transferred cells had to be challenged in the recipients within 1 day after cell transfer: when challenge was delayed for 5 days or longer, responsiveness returned. The failure of cells from recently primed donors to respond to the priming antigen on adoptive transfer could be overcome by supplementing with normal spleen cells, but not with thymus alone or bone marrow alone. This implied that unresponsiveness occurred at the levels of both T and B lymphocytes, and was not due to a suppressive influence exerted by T cells. Further work is in progress to determine the mechanism of this transient state of specific unresponsiveness.

Animals↗

Cadaverine in bacteriophage T4.

Cadaverine was found in bacteriophage T4 when the host cells of Escherichia coli K-12 were grown in complex media and aerated by agitation. Only traces of cadaverine were found if the host was grown and agitated in synthetic medium or was aerated by vigorous bubbling in a complex medium. When the host cells were grown anaerobically in a complex medium, cadaverine became the major polyamine in the progeny phage. The polyamine content comprised 80% cadaverine, 14% spermidine (or its recently discovered homologue, N-3-aminopropyl-1, 5-diaminopentane), and the remainder putrescine. The conditions that favored appearance of cadaverine are known to be required for induction of lysine decarboxylase. It was shown that lysine was the sole source of bacterial cadaverine.

Aerobiosis↗