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J Sprent

Publications and source records attributed to J Sprent.

At least 217 records · Page 12Linked to original sources
PubMed1975

Tolerance to histocompatibility determinants in tetraparental bone marrow chimeras.

Tetraparental bone marrow chimeras were produced by injecting lethally X-irradiated F1 hybrids with relatively high numbers of T-cell-depleted bone marrow cells from both allogeneic parental strains. The mice survival in excellent health and showed a stable, approximately 50:50 (parent:parent), lymphoid cell chimerism lasting for at least 7 mo after irradiation; regeneration of host-type hemopoietic cells was very limited. Thymus, lymph node, and thoracic duct lymphocytes showed specific unresponsiveness to host mixed leukocyte reaction (MLR) determinants. Similarly specific tolerance to H-2 antigens of host type was demonstrated in spleen and lymph node. No suppressor cells could be demonstrated in either system and blocking serum factors could not be found. The results suggest specific deletion of functional T cells reactive to host-type MLR and cell-mediated lympholysis determinants.

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PubMed1975

Five types of lymphocytes (Ig-theta-, Ig-theta+weak, Ig-theta+strong, Ig+theta- and Ig+theta+) characterized by double immunofluorescence and electrophoretic mobility. Organ distribution in normal and nude mice.

The simultaneous detection of Ig and theta on the surface of mouse lymphocytes permits the detection of four cell types (Ig-theta-, Ig-theta+, Ig+theta-, and Ig+theta+) which also have distinct electrophoretic profiles. All types are present in variable proportions in all lymphoid organs studied. Results obtained in congenitally athymic nude mice and in T-deprived mice define a new type of lymphocyte, the Ig-theta+weak. This cell is non-recirculating, Ig-, with a low density of theta and a slow electrophoretic mobility. It is a candidate for a T-committed prethymic cell.

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PubMed1974

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.

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PubMed1974

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.

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PubMed1973

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.

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