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M Chofflon

Publications and source records attributed to M Chofflon.

12 recordsLinked to original sources
PubMed1991

[HTLV-I/II in Switzerland: apropos of 4 case reports].

HTLV-I/II (human T-cell lymphotropic virus type I and II) infection is endemic in South Japan, Subsaharan Africa, the Caribbean and in regions of South America and of the United States. The infection almost always remains asymptomatic but is also associated with two distinct diseases: tropical spastic paraparesis (TSP), and adult T-cell leukemia (ATL). Although very rare in Europe, HTLV-I/II infection may occur in patients originating from endemic areas. We report the cases of four patients seropositive for HTLV-I/II, all of them living in Switzerland. Three of them originate from Zaire; the fourth is a Swiss female married to a Taiwanese. One patient has TSP; one has pyramidal signs along with systemic vasculitis-associated neuropathy; the third is HIV-position with stage III B infection, without symptoms of TSP or ATL; the last is entirely asymptomatic.

Adult↗
PubMed1991

Interleukin-1 corrects the defective autologous mixed lymphocyte response in multiple sclerosis.

Patients with chronic progressive multiple sclerosis (MS) have alterations of T cell regulation that can be measured by in vitro assays and include decreases of the autologous mixed lymphocyte reaction (AMLR). Whether a defect in cytokine secretion was involved in the altered AMLR was investigated in 29 MS patients and 13 age- and sex-matched controls. The response of CD4+ T cell populations to irradiated non-T cells was decreased in MS as compared to control subjects. As previously reported, decreases in the AMLR were similarly observed with whole T cells of MS subjects as compared to controls. The addition of recombinant interleukin (IL)-1 to cultures of either whole T cells or CD4+ T cells with irradiated non-T cells in the AMLR corrected the immune defect in subjects with MS but had no effect on the AMLR in control subjects. In contrast, addition of rIL-2 or rIL-4 to the AMLR did not correct the decreased AMLR in MS patients as compared to controls. The lymphokines IFN-gamma and TGF-beta 2 both decreased the AMLR in MS patients and controls while TNF had no effect. Further, the magnitude of the AMLR response corresponded to IL-1 secretion induced by LPS in the non-T cell population. These studies indicate that defects in IL-1 may be related to immune defects of suppression in MS patients. Selective correction of immunoregulatory defects using lymphokines or their inducers in subjects with autoimmune diseases such as MS may be possible.

CD4-Positive T-Lymphocytes↗
PubMed1991

Predictive value of anti-GM1 ganglioside antibodies in neuromuscular diseases: a study of 180 sera.

The incidence of anti-GM1 antibodies in the serum of 104 patients with neurological diseases, 35 patients with non-neurological diseases (NND) and 41 normal controls was determined by enzyme-linked immunosorbent assay (ELISA). Anti-GM1 antibodies were found in 90% of patients presenting with a motor neuropathy (all except one had multifocal conduction blocks). A large proportion (60%) of these patients displayed high antibody titer ranging from 101 to 788. A low incidence of anti-GM1 antibodies was found in the other groups of patients, i.e. 21% of amyotrophic lateral sclerosis (ALS), 26% of other neurological diseases (OND) and 23% of NND. High antibody titers ranging from 106 to 260 were found in two (5%) ALS patients, one (2%) OND patient (myasthenia gravis), and one (3%) NND patient (Waldenström's disease). This study shows that high titers of anti-GM1 antibodies are found in a large proportion of patients with motor neuropathy with multifocal conduction blocks. This argues for a possible autoimmune origin of this neuropathy. We suggest that anti-GM1 antibody determination should be included systematically in the evaluation of all patients with motor neuron diseases and predominantly motor neuropathies.

Adult↗
PubMed1989

Mechanisms of immune memory. T cell activation and CD3 phosphorylation correlates with Ta1 (CDw26) expression.

The Ta1 (CDw26) Ag distinguishes a subset of circulating T lymphocytes that is the major population proliferating to recall Ag challenge. Unlike receptors for growth factors such as IL-2 and transferrin, the Ta1 Ag is present on T cell lines and clones irrespective of cell cycle. The appearance of Ta1 on T cells that respond to recall Ag allowed us to investigate activation requirements that may be associated with T cell immune memory. Ta1+ peripheral blood T cells were induced to proliferate by mAb recognizing either the invariant chains of the TCR, or by pairs of mitogenic antibodies directed to the CD2 molecule. In contrast, Ta1- cells were not stimulated by these antibodies. In addition, Ta1-cells did not proliferate maximally after addition of the phorbol ester PMA in combination with the calcium ionophore Ionomycin, suggesting that the intracellular targets of these agents may not be fully active. Anti-CD3-induced elevation of intracellular calcium levels was equivalent in the two subpopulations, suggesting that calcium mobilization mechanisms were intact. In contrast, PMA-induced phosphorylation of TCR CD3 chains was significantly greater in Ta1+ cells as compared to Ta1- T cells. Taken together, our results indicate that Ta1 expression, which is associated with T cell activation and memory, may be causally related to TCR and CD2-mediated activation mechanisms. The PMA inducible TCR phosphorylation in Ta1+ memory cells associated with their increased ability to proliferate after CD3/TCR or CD2 stimulation suggests that intracellular phosphorylation events may be causally associated with T cell immune memory.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Decrease of suppressor inducer (CD4+2H4+) T cells in multiple sclerosis cerebrospinal fluid.

T-lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis are predominantly CD4+ (inducer) as opposed to CD8+ (suppressor/cytotoxic) T cells. The CD4+ lymphocytes can be subdivided into populations that express high densities of the CDw29 (4B4) determinant and have helper inducer function or express high densities of CD45R (2H4) determinant and have suppressor inducer function. In the present study, we characterized the nature of these CD4+ T cells in the cerebrospinal fluid of patients with multiple sclerosis by performing flow cytometric analysis on paired samples of blood and cerebrospinal fluid. There were significantly lower percentages of CD4+2H4+ T cells in the cerebrospinal fluid than in the peripheral blood (p = 0.001, paired t test). In contrast, there were increased percentages of helper inducer (CD4+4B4+) T cells in the cerebrospinal fluid (p = 0.001, paired t test), compared with the peripheral blood. Analysis of subjects with other inflammatory disorders of the central nervous system did not show significant decreases in CD4+2H4+ T cells in cerebrospinal fluid, though in some, decreases were also observed. These results indicate that the CD4+ T cells in the cerebrospinal fluid of patients with multiple sclerosis are predominantly helper inducer, as opposed to suppressor inducer T cells, and that the relative decrease of suppressor inducer cells in the peripheral blood of multiple sclerosis patients is not due to their migration to the cerebrospinal fluid. Furthermore, the increased numbers of helper inducer cells in the cerebrospinal fluid may contribute to local autoimmune processes in the central nervous system compartment of multiple sclerosis patients.

Humans↗
PubMed1989

Inflammatory cerebrospinal fluid T cells have activation requirements characteristic of CD4+CD45RA- T cells.

It has long been recognized that T cells in the cerebrospinal fluid (CSF) and other inflammatory compartments cannot be stimulated by mitogen and the reason for this has remained unknown. This question was investigated using mononuclear cells (MNC) isolated from the CSF of subjects with multiple sclerosis and other inflammatory brain diseases which predominantly express the CD4 and CDw29 but not CD45RA determinants. CSF and blood cells were stimulated by either the CD3/T cell receptor complex, the CD2 activation pathway, calcium ionophore, or an activator of protein kinase C, phorbol myristate acetate (PMA). CSF MNC proliferated less than blood MNC following stimulation by phytohemagglutinin in subjects with inflammation in the CSF, but not in subjects with non-inflammatory CNS diseases. Moreover, CSF MNC were not induced to proliferate through stimulation of the CD2 pathway by anti-T11(2) + anti-T11(3) monoclonal antibodies (mAb). This was not due to defects in either interleukin 2 receptors, interleukin 2 secretion, or to T cell pre-activation in vivo. Instead, the refractory activation state of inflammatory CSF T cells was corrected by PMA. That CSF contains predominantly CD4+CDw29+CD45RA- cells suggests that PMA may be co-stimulatory with anti-CD2 mAb to activate this population of T cells. This was confirmed in experiments with sorted T cells from normal subjects. These data suggest that the inability of mitogens or anti-CD2 mAb to stimulate inflammatory CSF T cells, which can be corrected by an inducer of protein kinase C, is related to the relative absence of CD4+CD45RA+ cells in the CSF. Alterations of protein kinase C and protein phosphorylation may exist in inflammatory T cell populations that regulate the immune response.

Antigens, Differentiation↗
PubMed1988

Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4+ 2H4+) T cells in multiple sclerosis.

A consistent immunological finding in patients with progressive multiple sclerosis is a loss of functional suppression. We have recently found decreases in suppressor inducer T cells in progressive multiple sclerosis as measured by two-color immunofluorescence using differentiation markers CD4 and 2H4. In the present study, we examined the relationship between functional suppression and circulating CD4+ 2H4+ T cells using a two-stage assay. (1) T cells were stimulated for 7 days with irradiated non-T cells (autologous mixed lymphocyte reaction [AMLR]) and harvested. It has previously been shown that suppressor T cells are generated during the course of the AMLR. (2) The AMLR-generated suppressor T cells were then incubated with mononuclear cells plus pokeweed mitogen, and immunoglobulin (Ig) synthesis was measured. There was less AMLR-induced suppression of IgG synthesis in patients with progressive multiple sclerosis as compared with normal subjects and patients with other neurological diseases. More importantly, there were significant correlations between decreases in circulating CD4+ 2H4+ cells and the AMLR (p = 0.009). Thus, the decreases in functional suppression and the decreases in the AMLR in multiple sclerosis appear tightly linked to CD4+ 2H4+ cells, and their measurement provides a means to monitor suppressor function phenotypically. Decreases in suppressor inducer T cells may in part explain immunoregulatory abnormalities observed in multiple sclerosis.

Biological Assay↗
PubMed1986

[Persistent generalized lymphadenopathies in homosexuals and drug addicts: changes in humoral and cellular immunity].

In two groups of subjects at risk for acquired immune deficiency syndrome (AIDS), homosexual males and intravenous drug users with persistent generalized lymphadenopathy, humoral and cell-mediated immunity were compared. A small group of patients with definite AIDS were also studied. It was found that levels of immunoglobulins, serological markers for virus and other infections, cell-mediated immunity and histology of lymph nodes were similar in homosexuals and drug users, whereas the lymphocyte sub-populations differed completely. The number of T4+ lymphocytes was markedly decreased in homosexuals but normal in drug users; the number of T8+ lymphocytes was much higher in drug users than in homosexuals. This discrepancy may explain the extremely low prevalence of AIDS cases observed among Swiss drug users as compared with the high frequency noted among homosexuals.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Altered functions of peripheral blood monocytes in homosexual males and intravenous drug users with persistent generalized lymphadenopathy.

Persistent generalized lymphadenopathy (PGL) is observed predominantly in subjects at risk of developing AIDS. Twenty-seven individuals belonging to such groups: twelve homosexual males and fifteen intravenous drug users, were investigated for immunological abnormalities with particular attention to monocyte functions. They were compared with five AIDS patients. Twenty out of twenty-two individuals had anti-LAV/HTLV-III antibodies and most had abnormalities characteristic of AIDS: polyclonal hypergammaglobulinemia, decreased cell-mediated immunity, inverted T-cell helper/suppressor ratio and histological alterations of lymph nodes. As for peripheral blood monocyte functions, phagocytic capacity and production of O2- were normal and bactericidal capacity was decreased. Monocytes cultured in the presence of concanavalin A produced less PGE2 and more IL-1/MCF than normal monocytes. Similar abnormalities were found using monocytes from AIDS patients. These data suggest that monocytes from patients with PGL have functional alterations that may be either intrinsic or secondary to lymphocyte dysfunction(s); these alterations do not account for the decreased capacity of lymphocytes to respond to mitogens but may explain the uncontrolled activation of B cells.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Tumor necrosis factor alpha production as a possible predictor of relapse in patients with multiple sclerosis.

No biological parameter is currently available as a specific marker of multiple sclerosis (MS) activity. The aim of this study was to determine whether an evolution of the neurological disability is associated with a modified profile of cytokine production. Clinical disease activity was quantitated by the Kurtzke's expanded disability status scale (EDSS). Whole blood was stimulated with phytohemagglutinin (PHA) for 2 hours at 37 degrees C and the activated plasma was assayed for Tumor necrosis factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1 beta). Relapsing-remitting MS patients enduring a relapse (RRMS, in relapse) (721 +/- 58 pg/ml, n = 27) and chronic progressive MS (CPMS) patients (516 +/- 33 pg/ml, n = 17) had an higher TNF-alpha production capacity as compared to healthy subjects (143 +/- 25 pg/ml, n = 17), RRMS, stable patients, (123 +/- 11 pg/ml, n = 26) or other neurological diseases (OND) without immunological or inflammatory disease in the peripheral immune compartment (131 +/- 24 pg/ml, n = 14) (t test: p < 0.0001). IL-1 beta production was also significantly higher but to a lesser extent in the same conditions. Concentration of TNF-alpha was also found to be significantly higher in the cerebrospinal fluid (CSF) of CPMS patients (199 +/- 7.8 pg/ml, n = 7, p < 0.0001) but also in RRMS, in relapse (149 +/- 5.7 pg/ml, n = 11, p < 0.05) as compared to RRMS, stable (130 +/- 4.4 pg/ml, n = 7) or OND without inflammatory or immunological disease of the central nervous system (CNS) (142 +/- 6.2 pg/ml, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗