Jean Michel Goust

Abnormal T cell subpopulations and circulating immune complexes in the Guillain‐Barré syndrome and multiple sclerosis

Immunologic studies were performed in 21 patients with multiple sclerosis(MS) and 16 with the Guillain-Barré syndrome (GBS). Levels of thymus-derived (T) cells measured by “total” and “active” rosette formation between sheep erythrocytes and peripheral blood mononuclear cells (TEt, TEa) were within normal limits in all the patients, with the exception of four GBS patients, including one who also had received chemotherapy for lymphoma and three who were receiving steroids. When lymphocytes from the 21 patients were incubated with the bone-marrow-derived (B) lymphoblastoid cell line PGLC-33H, there were, for 12 of 18 MS patients and 11 of 16 GBS patients, significant decreases in a subpopulation of peripheral blood T lymphocytes that form “PGLC rosettes” (PGR) with the PGLC-33H cells. (Peripheral blood T cells from normal individuals formed PGR with 23.9 ± 3.8 percent of PGLC-33H cells.) Using the l25 I-Clq binding assay, immune complexes were detected in the serum of 14 of 19 MS patients and 15 of 16 GBS patients. An association between increased C1 q binding and decreased PGR values was found in 10 of 18 MS patients and 12 of 17 GBS patients. The results suggest that in both diseases the etiology may involve a decrease in the subset of T cells that bind to the IgM-producing cell line PGLC-33H, in association with the appearance of circulating immune complexes containing the infectious viral agent.

Cyclic variations in white cell subpopulations in the human menstrual cycle: Correlations with progesterone and estradiol

Cyclic variations in white cell subpopulations were studied in serial blood samples from 18 female volunteers (14 ovulatory and 4 nonovulatory cycles) and 2 males. Total white blood cells (WBC), lymphocytes, total and active T cells (TEt, TEa), monocytes, and granulocytes were counted, and levels of estradiol (E2), progesterone, and luteinizing hormone (LH) were measured. In the ovulatory cycles, lymphocyte counts at midcycle (Day 0) reached a minimum, coinciding with the maximum level of E2 peak (35 ng%). In daily samples, the minimum lymphocyte counts coincided with the preovulatory E2 surge (P < 0.01). Similar but less significant negative correlations (P < 0.05) were found between E2, WBC, and TEt. In contrast, TEa did not show cyclic variations. Monocyte and granulocyte counts were significantly higher in the luteal than in the follicular phase (P < 0.05); their pattern followed closely that of progesterone (P < 0.05) but not of E2. Daily evaluations of hematocrit, hemoglobin content, red blood cell count, and mean corpuscular volume failed to show cyclic variations. For the females with nonovulatory cycles and for the males studied (with sex steroid profiles corresponding to the follicular phase), no cyclic variations were found in white cell subpopulations.

The interaction of CD2 with its LFA-3 ligand expressed by autologous erythrocytes results in enhancement of B cell responses

The addition of autologous erythrocytes to unfractionated human mononuclear cell cultures results in enhancement of B cell responses to antigens and mitogens. This costimulating effect of red cells is abrogated by their preincubation with anti-LFA-3 monoclonal antibody. Preincubation of mononuclear cells with anti-CD2 monoclonal antibodies (anti-Leu 5b, OKT11, used singly) has a down-regulating effect on B cell activation and no enhancement of B cell responses is seen when red cells are added to anti-CD2-treated cultures. These results demonstrate a functional effect on B cells of the interaction between the CD2 molecule on T lymphocytes and its natural ligand, LFA-3. The precise mechanism by which this costimulating effect on B lymphocytes takes place is unclear. The study of T cell populations and T cell activation markers shows that the addition of erythrocytes causes a small but reproducible increase in the number of cells expressing the IL-2 receptor and the addition of IL-2 enhances the response of mononuclear cells to antigenic stimulation in the presence of erythrocytes. However, the supernatants of mononuclear cell cultures stimulated with pokeweed mitogen in the presence of autologous erythrocytes show decreased levels of IL-2, compared to supernatants of cells stimulated with pokeweed mitogen alone. The same supernatants show increased levels of interferon-gamma, but the addition of this lymphokine to cultures stimulated with pokeweed mitogen has no potentiating effect. It is possible that the effect of erythrocytes is mediated by other growth and/or differentiation factors, and additional studies will be required to clarify this point.

Pattern and concentration of IgG in cerebrospinal fluid in neurosarcoidosis

Fteports have suggested that the pattern of CSF IgG dif-ferentiates neurosarcoidosis from multiple sclerosis. We examined CSF and serum of 7 patients with neurosarcoidosis to determine concentrations of IgG and al-bumin and the presence of oligoclonal bands. Our results showed that neurosar-coidosis may have associated abnormalities of IgG synthesis and oligoclonal bands present in CSF, but without a consistent pattern.

Active and Suppressor T Cells: Diminution in a Patient with Dyskeratosis Congenita and in First-Degree Relatives

Active, total and nonspecific suppressor T cells were studied in a 15-year-old black male with dyskeratosis congenita syndrome, a precancerous mucosal disease, and in 7 siblings and several other relatives in three generations. The propositus and 1 elder sister, products of a second-cousin marriage, died with dyskeratosis congenita. The mother had dermatomyositis, and the maternal grandmother and her sister reportedly had rheumatoid arthritis. Studies of available siblings, father, and grandparents revealed a high incidence of deficiency in number of active and/or suppressor T cells, sometimes severe enough to result in a decrease in total T cells. The patient had many stigmata of precocious aging, as did the sibling who died with the same syndrome. The laboratory data suggest that a defect in cell-mediated immunity, involving mainly or exclusively suppressor T cells, is associated with, and is presumably the cause of, precocious aging; perhaps an abiotrophy in this cell subpopulation results in physiologic aging.

Progressive multifocal leukoencephalopathy occurring with the acquired immune deficiency syndrome.

A 33-year-old homosexual man with symptoms and signs of a focal brain process was subsequently found to have an acquired immune deficiency syndrome (AIDS) with biopsy-proven progressive multifocal leukoencephalopathy. This report reemphasizes the association of progressive multifocal leukoencephalopathy with AIDS and probably is best viewed as another example of an opportunistic CNS infection complicating deficient cell-mediated immunity.

Chorioretinitis with a combined defect in T and B lymphocytes and granulocytes: A new syndrome successfully treated with dialyzable leukocyte extracts (transfer factor)☆

A patient with immune deficiency, recurrent pyogenic infections and active chorioretinitis is described; in addition to agammaglobulinemia, both quantitative and qualitative T-cell deficiencies were documented. Furthermore, the patients granulocytes (polymorphonuclear leukocytes), although normal in their bactericidal capacity for Staphylococcus, responded poorly to both leukocyte migration inhibition factor and neutrophil immobilizing factor obtained from normal cells. The immunologic features of this patient appear to comprise a new syndrome. Remarkable diminution of the ocular lesions and increased visual acuity occurred within two months after the initiation of therapy with dialyzable leukocyte extracts (transfer factor). Concurrent testing of the patients cell-mediated immunity showed increased numbers of circulating T lymphocytes and improved T-cell function following dialyzable leukocyte extract [DLE] therapy. The dramatic clinical results indicate that similar therapy may prove to be beneficial in other patients with chorioretinitis and T-cell deficiency.

T Cells, Precocious Aging, and Familial Neoplasia

A 15-year-old girl presented with precocious aging and was found to have low levels of active and total T cells. Family history revealed a high familial incidence of cancer on both the maternal and paternal sides, and activ T cell levels were found to be low in several living family members. The patient developed osteogenic sarcoma 13 months after initial study. Since our previous studies have reported low active and total T cells in patients with cancer, the present results suggest that subjects with low active T cells should be monitored frequently to detect possible neoplasia in it early stages. They also suggest that impaired cellular immunity in humans is associated with, if not the cause of, accelerated aging.

IN VITRO ASSAY FOR TRANSFER FACTOR BY MEANS OF LEUKOCYTE MIGRATION TEST (LMT)

Publisher Summary This chapter discusses the in vitro assay for transfer factor by means of leukocyte migration test (LMT). Suitable donors were selected in the family and from normal volunteer blood donors after their reactions to measles virus in the LMT were found positive. TFd was prepared and quantified. The children selected for TFd therapy were injected with at least 2 mg of Orcinol-reactive material and the injections were repeated the results of LMT, disappearance of CMI to MV indicating the need for a new series of shots. TFd was left over night with the cells at high concentration and it appeared very soon that a shorter incubation time was necessary, together with a lower concentration of TFd, because a direct toxic effect of TFd was obvious, MIA being around 0.60 for 0.95 > MIB > 1.05. There was no difference between cells incubated for 1 h at 37°C, and cells immediately placed in capillary tubes at the end of the fourth wash.

QUANTITATION OF TRANSFER FACTOR

Publisher Summary This chapter elaborates the quantitation of transfer factor (TF). White blood cells from peripheral blood of volunteer normal donors were obtained by leukopheresis and pooled to produce TFd from at least 5 × 10 lymphocytes. CMI responses of the donors were estimated by the leukocyte migration test and by skin testing against measles virus, diphtheria toxoid and tuberculin PPD. Monitoring of dialysis by the optical density at 260 and 280 nm indicated approximately the yield of a given batch, also allowing change of the dialysis liquid if the slope reached a plateau or if the OD260 exceeded 1500. This was later confirmed by measurement of orcinol-reactive material (ORM) and protein, demonstrating that more than 90% of the dialyzable material is obtained at 18 h, total exhaustion being reached after 24 h, with one change of the dialysis liquid. There is a discrepancy between proteins and ORM, the latter dialyzing faster than the former and 65 to 75% of the total yield of ORM is obtained at 6 h, compared with only 35 to 66% of the proteins.