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Biomedical subjects

G Milon

Publications and source records attributed to G Milon.

At least 73 records · Page 4Linked to original sources
PubMed1988

Early influx of Listeria-reactive T lymphocytes in liver of mice genetically resistant to listeriosis.

Murine listeriosis is a classical model for investigating mechanisms of cellular immunity, which involves interaction of macrophages and T lymphocytes. The early course of this experimental infection is under control of a limited number of genes in the murine host. In the present study, we asked whether the early efficient control of bacterial growth in the liver of resistant mice is related to the expression of a more rapid specific immune response in this organ than in susceptible mice. Therefore, we compared the frequencies of Listeria monocytogenes-reactive T cells in blood, spleen, and liver of resistant C57BL/6 and susceptible C3H/He Past mice after i.v. injection of a high dose of Listeria (9 x 10(5) CFU). T cells were titrated through their ability to locally transfer a delayed-type hypersensitivity reaction to viable L. monocytogenes, an effector function potentially relevant to the early step of protective mechanisms. We observed (1) a 9- and 4-fold increase by day 1 in the frequency of Listeria-reactive transfer units in the blood of C57BL/6 and C3H mice, respectively, (2) no increase in the number of Listeria-reactive transfer units in the spleen of 2-day infected mice of both strains, and (3) a 90-fold increase, at day 2, in the number of Listeria-reactive transfer units in the liver of resistant C57BL/6 compared with only a 9-fold increase in the liver of susceptible C3H/He. These results suggest that the ability of C57BL/6 mice to control the early bacterial growth (0 to 48 h) in their liver, may be related to a rapid influx of L. monocytogenes-reactive T lymphocytes.

Animals↗
PubMed1987

L3T4+ T cells able to mediate parasite-specific delayed-type hypersensitivity play a role in the pathology of experimental Chagas' disease.

During the chronic phase of infection with the parasite Trypanosoma cruzi, mice develop inflammatory lesions in the heart and skeletal muscles, as well as in peripheral nerves and the liver. We demonstrated the presence, in the blood of chronically infected mice, of L3T4+ T cells able to transfer a specific T. cruzi delayed-type hypersensitivity (DTH) reaction. Transfer of the chronic inflammatory lesions was obtained by injecting Lyt-2+-depleted lymphocytes from either lymph node or blood of infected mice. T cell lines were established from the chronically infected mice by culturing peripheral blood lymphocytes or lymph node cells with either T. cruzi extracts (TC) or mouse peripheral nerve extracts (PN). Those cell lines that presented an L3T4+ phenotype were also able to specifically transfer a local DTH reaction to naive recipients. Examination of the antigen specificities of these TDTH lines revealed three types: those that mediated a DTH reaction to TC, those that responded to both TC and PN and those that provoked a DTH response when injected with subinflammatory doses of an irrelevant antigen. Some of the lines, when injected into the sciatic nerve of naive recipients, provoked demyelination of the type observed in chronically infected animals. These results suggest that T. cruzi and the host nervous system share common epitopes that can be recognized by TDTH cells.

Animals↗
PubMed1987

Involvement of specific Lyt-2+ T cells in the immunological control of experimentally induced murine cutaneous leishmaniasis.

The involvement of Lyt-2+ T cells in the immunological control of cutaneous leishmaniasis was assessed by studying the course of the disease in mice in which the number of these cells was reduced by treatment with anti-Lyt-2 monoclonal antibody (mAb). Administration of anti-Lyt-2 mAb exacerbated Leishmania major-induced cutaneous lesions in both genetically resistant and susceptible mice. This effect correlated with a drastic reduction in the number of specific Lyt-2+ T cells generated during infection. These results, together with the observation that resistant mice possess higher numbers of specific Lyt-2+ T cells in lymph nodes draining their lesions than susceptible mice, 3 weeks after infection, indicate that Lyt-2+ T cells also play a role in the immunological control of Leishmania major-induced lesions.

Animals↗
PubMed1986

Higher frequency of Leishmania major-specific L3T4+ T cells in susceptible BALB/c as compared with resistant CBA mice.

In previous studies, we reported that a) the adoptive transfer of parasite-specific L3T4+ T cells enhanced rather than inhibited the development of lesions induced by Leishmania major in normal BALB/c mice, and b) the depletion in vivo of L3T4+ T cells by administration of anti-L3T4 monoclonal antibody reversed the susceptibility of BALB/c mice to L. major. To further assess the role of specific L3T4+ T cells in the development of lesions induced by L. major in BALB/c mice, the frequency of parasite-specific T cells capable of mediating specific delayed-type hypersensitivity (DTH) reactivity was determined, by limiting dilution analysis, in the lymph nodes draining the lesions of susceptible (BALB/c) and resistant (CBA) mice. The numbers of L. major-specific DTH-mediating T cells was found to be substantially increased in the lymph nodes of infected BALB/c mice as compared with CBA mice. Moreover in CBA mice, analysis of the cell surface phenotype of the L. major-specific DTH-mediating T cells showed that these cells were equally represented in the L3T4+, Lyt-2-, and L3T4- Lyt-2+ subsets, whereas the majority of these cells in BALB/c mice expressed the L3T4+ Lyt-2- surface phenotype.

Animals↗
PubMed1986

Apparent increased sensitivity of mice to tuberculin by adding a non-specific inflammatory agent to the antigen.

The delayed-type hypersensitivity (DTH) reaction at the site of tuberculin injection in immunised animals depends on the presence of sentisitised T-lymphocytes which interact with the antigen and recruit non-specific phagocytic cells. The intensity of DTH reaction was found to be related to the non-specific inflammatory stimulus created by antigen injection. The early plasma protein extravasation which occurred 0.5 of an hour after antigen injection was correlated with the intensity of DTH reaction measured 18 hours later. The addition to tuberculin of a non-specific inflammatory agent (concanavalin A or sheep red blood cells) in a dose range without clinical inflammatory effect increased the apparent potency of tuberculin by a factor 1000.

Animals↗
PubMed1986

Control of hemopoiesis in mice by sensitized L3T4+ Lyt2-lymphocytes during infection with bacillus Calmette-Guérin.

When injected intravenously with bacillus Calmette-Guérin (BCG; 10(7) viable units), C57BL/6 mice rapidly develop a transient anemia associated with an increased number of granulocytes and monocytes, whereas C3H/He mice do not. Because these two features are lacking in C57BL/6 nude mice we postulated that T lymphocytes can regulate hemopoiesis during infection. To assess further the role in hemopoiesis of T lymphocytes present in bone marrow of C57BL/6 and C3H/He mice, the frequency of BCG-specific T lymphocytes and their surface marker phenotype were determined by limiting dilution analysis and use of monoclonal antibodies. The number of BCG-specific T lymphocytes was estimated to be 50- to 100-fold higher in bone marrow of C57BL/6 than in that of C3H/He mice. Although L3T4+ Lyt2-and L3T4- Lyt2+ BCG-specific T lymphocytes were generated in mice of both strains, in C57BL/6 mice L3T4+ cells were induced preferentially from day 1 through day 5 after infection in correlation with hemopoietic changes. The relation between T-cell immune response and hemopoietic changes was substantiated by results obtained after in vivo treatment with monoclonal antibodies. Selective depletion of L3T4+ T cells by in vivo injection of anti-L3T4 monoclonal antibodies (GK 1-5) inhibited the development of the anemia and the related increased production of phagocytes in C57BL/6 mice receiving BCG.

Anemia↗
PubMed1985

T-dependent production and activation of mononuclear phagocytes during murine BCG infection.

Mice infected with a high dose of viable Bacillus Calmette Guerin (BCG) intravenously offer an interesting model to study regulatory functions of T cells on hemopoiesis. The proposition that T lymphocytes may play such a regulatory role was tested in nu/nu and two genetically different strains of mice: while the hemopoiesis of C3H/He mice remained unchanged during BCG injection, that of infected C57BL/6 mice was rapidly and transiently modified towards increased production of phagocytes at the expense of the erythroid lineage. The number of BCG-specific T cells present in C57BL/6 bone marrow was 50-100 higher than that determined in C3H/He mice. Moreover, between day 0 and 5 of infection the majority of BCG-specific T cells in C57BL/6 animals were of the L3T4+ Lyt2- surface phenotype. An attempt was made to identify the nature of the T cell product(s) able to activate young bone marrow-derived macrophages to render them non-permissive to growth of BCG.

Animals↗
PubMed1984

A new assay suitable for enumeration of murine progenitors of granulo-monocytes and for rapid automated assessment of granulo-monocyte growth factors.

A simple and reproducible assay is described for enumerating the progenitors of granulocytes (G) and monocytes (M) present in either the bone marrow or spleen of mice. This assay is based upon the plating of different dilutions of test cells in the wells of Terasaki plates. Negative and positive wells for presence of G and M are scored 7 days later. Minimal estimates of GM progenitors frequency are obtained by analysis of the Poisson distribution relationship between the percentage of non-responding microcultures and the numbers of cells plated. This liquid microculture assay offers many advantages: (1) the ability to assay directly in situ at clonal level different enzymatic activities like non-specific esterase; (2) the ability to screen within 3 days the presence of GM growth factors by measuring the [3H]thymidine uptake of proliferating responsive cells.

Animals↗
PubMed1984

Cyclosporin A inhibits the delayed-type hypersensitivity reaction: impaired production of early pro-inflammatory mediator(s).

The effect of cyclosporin A (CsA) on the delayed-type hypersensitivity (DTH) elicited in mice by sheep red blood cells was investigated. Evidence is presented that a single injection of CsA adversely affects the inflammatory reaction. Sensitized T lymphocytes initiate the DTH reaction by their recruiting activity on phagocytic cells which infiltrate the cutaneous site of antigen deposition. CsA administration has no adverse effect on the recruitment of phagocytic cells at the site of the inflammatory reaction. The present studies show that CsA acts on specific T cells: (a) in adoptive transfer, T-DTH-mediating cells cannot elicit a response in mice treated with CsA 8 h before; (b) when collected 8 h after a single injection of CsA, T-DTH-mediating lymphocytes are no longer able to adoptively transfer the reaction. This conclusion is strengthened by in vitro studies: (a) the frequency of T-DTH-mediating lymphocytes is 50-fold decreased after a short in vitro incubation with CsA; (b) in vitro production by concanavalin A-activated lymphocytes of chemotactic pro-inflammatory mediator(s) is abolished in presence of CsA.

Animals↗
PubMed1983

Is the delayed-type hypersensitivity observed after a low dose of antigen mediated by helper T cells?

In mice receiving, i.v., a dose of antigen optimal for antibody response, no delayed-type hypersensitivity (DTH) reaction is detectable. In contrast, in mice receiving a dose of antigen too small to induce B cell activation, a DTH reaction is elicitable shortly and transiently after immunization. Using a sensitive titration assay of DTH-mediating T lymphocytes, this reciprocal relationship between antibody production and DTH responses was reinvestigated. The absence of peripheral DTH reactivity in mice primed i.v. with a high dose of antigen (10(9) heterologous red blood cells) does not result either from the absence of activation and clonal expansion of DTH-mediating cells or from induction of suppressive mechanisms but results from a decreased circulation of DTH-mediating cells. The present studies show that DTH-mediating cells disappear from blood to enter the spleen only when specific B lymphocytes are present and activated by a high dose of antigen. These results are compatible with the hypothesis that T cells activated by antigen can function either as helper cells for B lymphocytes or as DTH-mediating cells, depending on the environment they reach during their migration. In order to demonstrate that the same cell may support the two functions, monoclonal T lymphocytes were assayed for their helper function and for their ability to transfer a DTH reaction.

Animals↗
PubMed1982

Local adoptive transfer of skin delayed-type hypersensitivity initiated by a single T lymphocyte.

In vivo primed T cells injected in the footpad of naive recipients elicit a typical delayed-type hypersensitivity (DTH) reaction in the presence of their specific antigen. The values of the footpad swelling obtained after these transfers show a clear distinction between negative and positive responses. Serial dilutions of primed T cell populations allow the establishment of titration curves by limiting dilution analysis according to Poisson distribution. The single hit titration curve indicates that a unique cell type underlies the DTH reaction. Furthermore, by using cloned T cells it can be demonstrated that the transfer of a single cell is able to initiate a DTH reaction. The revelation of T cell activity at unit level needs an optimal dose of antigen mixed with the sampled cells.

Animals↗
PubMed1981

A delayed-type hypersensitivity reaction initiated by a single T lymphocyte.

In vivo primed T cells injected into the footpad of naïve recipients elicit a typical delayed-type hypersensitivity (DTH) reaction in the presence of their specific antigen. Serial dilutions of primed T cell populations were used in order to score positive and negative transfers. The values for the footpad swelling obtained after these transfers followed a bimodal distribution. This clear bimodal distribution with no overlapping between positive and negative transfers suggested that a single cell initiates the DTH reaction. Limiting dilutions of cloned T cells transferred with their antigen allowed us to demonstrate that a single cell is able to transfer a specific DTH reaction.

Animals↗