Extensive Ulcerative Colitis and Extraintestinal Manifestations in a Patient with Hiv Infection and Significant Cd4 T-Cell Lymphopenia

in Gastroentérologie Clinique et Biologique (1997), 21(11), 884-7

We report a heterosexual patient with HIV infection and a CD4 T-cell count of 0.45 x 10(9)/L who developed mild ulcerative proctitis, sacroileitis and oligoarthiritis. While he was treated with 5 ... [more ▼]

We report a heterosexual patient with HIV infection and a CD4 T-cell count of 0.45 x 10(9)/L who developed mild ulcerative proctitis, sacroileitis and oligoarthiritis. While he was treated with 5-aminosalicylic enemas, the patient rapidly developed severe pancolitis. An emergency colectomy without procetectomy was performed. A few months later, he suffered recurrence of ulcerative proctitis, aggravation of arthritic pain and developed anterior uveitis. All symptoms disappeared after proctectomy. There was no evidence for opportunistic infection or Kaposi's sarcoma. Antineutrophil cytoplasmic antibodies were positive and the HLA-B27 antigen was present. CD4 counts were lower during the phases of active disease than during remission. This case demonstrates that severe ulcerative colitis can occur in the presence of moderate T-cell defects. In view of a recent report of remission of Crohn's disease under comparable circumstances, it is possible that the extent of T-cell involvement in both diseases is radically different. [less ▲]

Further Characterization of Cytotoxic T Cells Generated by Short-Term Culture of Human Peripheral Blood Lymphocytes with Interleukin-2 and Anti-Cd3 Mab

in Cancer Immunology, Immunotherapy (1996), 42(6), 369-75

In this study we have specifically investigated the participation of T cells in the cytotoxic activity of peripheral blood lymphocytes (PBL) activated by interleukin-2 (IL-2, 50 U/ml) alone or in ... [more ▼]

In this study we have specifically investigated the participation of T cells in the cytotoxic activity of peripheral blood lymphocytes (PBL) activated by interleukin-2 (IL-2, 50 U/ml) alone or in combination with an anti-CD3 mAb (BMA030, 10 ng/ml, IgG2a). Purified CD3+ T cells, incubated in the presence of the anti-CD3 mAb for 4 days, mediated a cytotoxic activity against HL60 and U937 tumor cell lines. Several findings suggested the involvement of a redirected-cytotoxicity phenomenon, since the lytic process was restricted to target cell lines bearing the high-affinity Fc gamma receptor (Fc gamma RI) and T lymphocytes stimulated by IL-2 alone did not lyse these cell lines. Furthermore, anti-CD3 mAb F(ab')2, anti-CD3 IgG1 (UCHT1), phytohemagglutinin or staphylococcal enterotoxin A did not induce a similar cytotoxic activity in T lymphocytes. The cytotoxic process occurred in the presence of a very low level of anti-CD3 antibodies (in the nanomolar range). The cytotoxic activity of T cells stimulated by IL-2 or by IL-2 + BMA030, against OVCAR-3 cells (MOv18+ ovarian tumor cell line), was also compared in the presence of a bispecific antibody OC/TR, anti-CD3 x MOv18). The stimulation by IL-2 + BMA030 induced approximately a twofold higher cytotoxic activity than IL-2-activated T cells. This could be related to the state of activation of effector cells stimulated by IL-2 + BMA030, since the phenotypic analysis showed an increased proportion of T cells expressing several activation/differentiation markers (CD25, HLA-DR, CD45R0, adhesion molecules). These findings could be applied to the design of therapeutic protocols using anti-CD3 x antitumoral bispecific antibodies. [less ▲]

Morphological Changes of Thymus in Retrovirus-Induced Murine Acquired Immunodeficiency Syndrome (Maids)

in Pathology - Research & Practice (1995), 191(6), 506-12

The possible contribution of the thymus in the setting of acquired immunodeficiencies is still questioned. Here we report some new findings regarding a potential involvement of the thymus in mice infected ... [more ▼]

The possible contribution of the thymus in the setting of acquired immunodeficiencies is still questioned. Here we report some new findings regarding a potential involvement of the thymus in mice infected with RadLV-Rs, a viral mixture inducing murine acquired immunodeficiency syndrome (MAIDS). Thymi were sequentially removed, weighted and morphologically analyzed at different time intervals post-infection. Infection with RadLV-Rs led to a decrease in thymus weight mostly apparent from the fourth week. The first changes were seen at the third week as perivascular clusters of B-cells at the cortico-medullary junction. The ensuing process of atrophy mainly involved the cortex, while a mixed population of large T- and B-cells filled the medulla. These observations are discussed with regard to the pathological changes occurring in other lymphoid and non-lymphoid organs, in the context of the lymphoproliferation and immunodeficiency characterizing the disease, and by comparison with other models of retrovirus-induced immunodeficiencies. [less ▲]

Population dynamics of CD4+ T cells lacking Thy-1 in murine retrovirus-induced immunodeficiency syndrome (MAIDS).

in Scandinavian Journal of Immunology (1994), 39(2), 216-24

Increased numbers of CD4+ Thy-1- cells have been described in the spleen (SP) of mice with retrovirus-induced immunodeficiency (MAIDS). Since this phenotypic abnormality might have considerable functional ... [more ▼]

Increased numbers of CD4+ Thy-1- cells have been described in the spleen (SP) of mice with retrovirus-induced immunodeficiency (MAIDS). Since this phenotypic abnormality might have considerable functional importance, the expansion of the CD4+ Thy-1- subset in MAIDS was characterized further. CD4+ Thy-1- and Thy-1+ T-cells from infected mice expressed similar densities of CD3 and TCR alpha/beta. In contrast, the Thy-1- subset was uniformly CD44hi, even early in the disease when part of Thy-1+ cells were still CD44lo. The emergence of CD4+ Thy-1- cells occurred first in SP and lymph nodes and was observed later in thymus. The important fraction of CD4+ cells lacking Thy-1 normally present in Peyer's patches was only weakly modified. Despite the major expansion of the CD4+ Thy-1- phenotype, the proliferating fraction was not higher in this subset than in CD4+ Thy-1+ cells from infected mice. Persistence after hydroxyurea administration was identical in both subsets, indicating similar mean cell lifespans. Taken together, these results show that the major expansion of CD4+ Thy-1- T-cells in MAIDS is not ascribable solely to increased proliferation within this subset. Phenotypic analysis suggests that CD4+ Thy-1- cells result from the differentiation of Thy-1+ cells induced by activation signals related to retroviral infection. [less ▲]

Lymphocyte Lifespan in Murine Retrovirus-Induced Immunodeficiency

in Advances in Experimental Medicine and Biology (1994), 355

Impaired immune responses in diabetes mellitus: analysis of the factors and mechanisms involved. Relevance to the increased susceptibility of diabetic patients to specific infections.

in Diabète & Métabolisme (1992), 18(3), 187-201

The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear. The virtual absence of epidemiological studies of the independent risk ... [more ▼]

The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear. The virtual absence of epidemiological studies of the independent risk factors involved contrasts with the multitude of in vitro models focused on the metabolism and function of immune cells from diabetic patients. This review analyzes some of these models and their clinical relevance. The different levels of diabetes pathogenesis: genetic (Type 1), autoimmune (Type 1) and metabolic (Type 1 and Type 2) are responsible for immune abnormalities demonstrated in in vitro models. The participation of genetic and autoimmune factors has been mainly characterized on T lymphocyte function. The B8 DR3 haplotype is associated with several minor immunologic abnormalities in vitro. However, the high frequency of this haplotype in healthy individuals argues against its involvement in significant defects of antimicrobial immunity. Genetic deficiency of C4, present in 25% of Type 1 diabetic patients could, on the other hand, be responsible for opsonization defects against encapsulated pathogens. Several immunological abnormalities related to the autoimmune process preceding the onset of Type 1 diabetes mellitus, such as the depletion of memory CD4+ cells and the defective natural killer activity could transiently impair host defences against viral diseases. Several in vitro functional defects of the immune system have been correlated with the metabolic control of diabetic patients. This suggests the involvement of insulinopenia in some of the abnormalities observed. Insulinopenia-induced enzymatic defects have often been proposed to inhibit energy-requiring functions of phagocytes and lymphocytes. However, the relevance of this mechanism could be confined to patients with extremely severe metabolic abnormalities. The importance of systemic consequences of insulinopenia such as hyperglycaemia and ketosis has also been addressed. Usually, the defects induced in vitro by these factors are slight and require supraphysiologic concentrations of glucose or ketone bodies. Recent studies have shown abnormalities of signal transduction mechanisms in which insulinopenia itself and other factors such as circulating immune complexes could be involved. Despite numerous controversies, many in vitro studies of the immune cells of diabetic patients have demonstrated significant defects which bear quantitative similarities with abnormalities described in other immunodeficiency syndromes. Furthermore, several mechanisms have been proposed to link the different defects observed with the specific infections encountered in diabetic patients. [less ▲]

Greffes de moelle osseuse: bilan au CHU de Liege.

in Revue Médicale de Liège (1990), 45(6), 268-79

Experimental set up of a fast gel filtration technique for the determination of the binding of a chemically labelled form of tetrodotoxin to its solubilized receptor from excitable tissues

in Archives Internationales de Physiologie et de Biochimie (1984), 92