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Signal joint T cell receptor excision circles (sjTRECs) have been reported as a clinical marker to measure the potential for recovery of the immune system after immunosuppressive treatments. The aim of this study was to investigate the thymic regenerative potential in 55 human immunodeficiency virus (HIV)-1 infected (HIV+) and non-infected (HIV-) lymphoma patients, candidates for autologous stem cell transplantation (ASCT). Moreover, the possible associations between sjTRECs and other immunological and clinical parameters were examined. SjTRECs levels in peripheral blood mononuclear cells (PBMCs) were quantified by real-time polymerase chain reaction and T lymphocyte subsets were analysed by flow cytometry. Our data showed that sjTRECs were reduced in lymphoma patients compared to healthy controls, although a weak significant association between low sjTRECs levels and increasing age was maintained [odds ratio (OR) = 4·00; 95% confidence interval (CI) 1·09–17·17]. We found that different chemotherapeutic treatments seem to induce similar effects on the thymic reservoir, independently from their intensity (type and number of cycles of previous chemotherapy). Results from multivariate models including adjustment for patients' sex, type of lymphoma and type of chemotherapy showed that thymic output was independent from HIV infection (OR, 0·95; 95% CI 0·20–4·48). SjTRECs levels correlated with naive T cell subsets in overall lymphoma patients and after stratification by HIV infection ( r > 0·37). HIV replication should be maximally suppressed to properly evaluate thymic output by sjTREC markers. Our results suggested that de novo T cell generation is maintained partially in pretreated recurrent lymphoma patients, candidates for ASCT, and could contribute to restore the immune function after transplantation. [ABSTRACT FROM AUTHOR]

The kinetics and effects of in vivo spontaneous apoptosis and activation-induced cell death (AICD) upon CD4+ and CD8+ lymphocyte subsets and CD4 naive cell numbers were studied in HIV+ subjects with CD4 pretreatment values > 200/mm3, who were subsequently treated for 48 weeks with HAART alone or in combination with six cycles of subcutaneous IL-2. Irrespective of the type of treatment, patients showed a statistically significant increase in CD4 cell counts after 4 weeks, although the CD4 naive subset only increased significantly in the IL-2-treated subjects at the end of treatment. The percentage of CD4 cells undergoing spontaneous apoptosis and AICD was significantly reduced in all patients after 4 weeks and this reduction was maintained until the end of therapy; however, the level always remained significantly higher in comparison with healthy subjects. A statistically significant reduction in CD8 apoptosis levels required at least 24 weeks of therapy. Together these data suggest that a reduction in the level of apoptosis may contribute to the early rise in CD4 numbers measured after HAART, but that later on HAART is unable to improve further this biological parameter. Although the use of IL-2 had no additional effects on spontaneous apoptosis and AICD, it may be beneficial by stimulating a late increase in the numbers of CD4 naive cells in HIV-treated subjects. [ABSTRACT FROM AUTHOR]

We have evaluated the autoantibody pattern, the production of specific immunoglobulins against bacteria in the urinary tract and lymphocytes populations in peripheral blood of primary renal glycosuria patients. All the affected members present autoantibodies against various antigens. In nine patients immunofluorescence revealed antibody coated bacteria in urine specimens. Imbalances in lymphocytes subpopulations are also present, with a reduction of OKT8+ cells and an increase of B and natural killer cells. These results support previous observations about immunological abnormalities in these patients. [ABSTRACT FROM AUTHOR]

Fresh peripheral blood was obtained from HIV-infected subjects and from age-matched healthy controls. Single-, two- and three-colour How cytometry was performed using FITC-labelled MoAbs directed against the following TCR V β subfamilies: V2, V3, V5a, V5b, V5c, V6, VS, V12, V13.3, VI7, V19, alone or in combination with PE-labelled CD4, CD8, HLA-DR, CD28, CD38 und with Peridinin-chlorophyll A protein (PerCP)-conjugated CD8. The percentages of each Vβ subfamily did not differ in HIV+ patients compared with healthy controls. However, we were able to find in four patients (one CDC group II, one group III and two group IV) an expansion of a TCR V β subfamily (V3 in two, V5a and V19 in one patient). These cells were mainly CD8+. Three- colour flow cytometry allowed us to define that the expanded V β, CD8+ T lymphocytes were characterized by the low/intermediate expression of activation markers (HLA-DR, CD28, CD38). In some HIV+ patients there is an expansion of T cells expressing a TCR V β subfamily: the nature of this expansion may be related to factors that are still unknown, such as the genetic background of each individual and the antigenic specificity of T cells. These populations may be relevant in the host response to the virus and in disease progression. [ABSTRACT FROM AUTHOR]

The γδ T cell receptor (TcR) lymphocytes constitute 3-10% of human peripheral blood lymphocytes. Only a very small fraction of these cells is recognized by the δTCSl monoclonal antibody, directed against the Vδ1 chain of the receptor. We describe the immunological, virological and clinical data of a small group of seropositive subjects having high levels of γδ TcR T cells in the peripheral blood. Our flow cytometric studies show that most of these cells belong to the δTCS1+ (Vδ1+), CD8± (dim staining) subset. Patients with high γδ TcR T cell numbers were not characterized by the presence of an acute (IgM positive) or reactivated (as defined by high IgG titres against early antigen or IgA titres against viral capsidic antigen) Epstein-Barr virus infection. Cytomegalovirus infection was excluded by serological assays, and other herpesviral infections were not found after clinical examination. HIV p24 antigenaemia was present in two out of 11 subjects. AIDS patients had very high percentages of γδ TcR T cells. Altogether these data show that the selective expansion of δTCS1+ cells in HIV1 seropositive subjects is not related to some exogenous antigen stimulation, but may be related to peculiar pathologic processes involving the immune system. [ABSTRACT FROM AUTHOR]

The expression of phenotypic markers on T and B lymphocytes in long-term human immunodeficiency virus type 1 (HIV-I) seropositive, antigen negative patients, in seropositive, antigen positive individuals without AIDS and in seronegative intravenous drug abusers was examined by two colour flow cytometry. Seropositive, antigen postive patients showed decreased CD4+ lymphocyte numbers, causing lower CD4/CD8 ratios when compared to seropositive, antigen negative subjects. While CD4 CDw29+ (4B4) lymphocytes are selectively reduced in seropositive, antigen negative individuals, both CD4 CDw29+ and CD4 CD45R+ (2H4) lymphocytes are decreased when antigenaemia is present. An increased percentage of CD3 HLA DR+ activated T lymphocytes and of CD20+ (BI) Leu 8 negative activated B cells was seen in HIV-1 seropositive antigen positive patients. These results demonstrate that, in long-term seropositive individuals, antigenaemia is associated with peculiar phenotypic changes of lymphocyte subsets. [ABSTRACT FROM AUTHOR]

The prolonged generalized lymphadenopathy syndrome (PGL) has been considered a prodromal condition to the Acquired immunodeficiency syndrome (AIDS), but the clinical, virological and immunological characteristics of patients who will develop AIDS are not known. We report on the immunological profile of intravenous drug abusers with or without PGL in Northeastern Italy. We found a reduction of lymphocyte-absolute numbers with reversal of the T4/T8 ratio and decreased Leu-llb+ cells. The response to mitogens and natural killer activity are compromised in PGL patients. Neutrophil function is reduced both in drug abusers with or without lymphadenopathy. The serological investigations revealed a high prevalence of antibodies against HTLV III and the Epstein-Barr viruses. The recognition of immune dysfunction in the intravenous drug abusers appears to be important since these patients develop AIDS and these abnormalities may precede AIDS. [ABSTRACT FROM AUTHOR]

In most HIV-1-infected patients, clinical and immunological progression develops within a few years. Few infected people, termed long-term non-progressors (LTNP), remain healthy and immunologically stable for a long time. The factors governing the maintenance of this condition are not well known, but it is conceivable that CD8+ lymphocytes, cells that play a central role in controlling in vitro HIV replication, may have a part in vivo in this process. The aim of this study was to characterize the phenotypic profile and the cytokine production of CD8+ cells in a group of LTNP patients who had stable CD4+ cell counts (>500/mm3) for at least 7 years. Their CD8+ absolute numbers were similar to a control group composed of HIV-1+ patients who have a progressive decline of their CD4+ cell counts. However, our multiparameter immunofluorescence studies show that a clinical and immunologically stable condition is associated with the presence of a CD28+, CD95 strongly positive CD8+ population, while disease progression is marked by the CD28-D95+CD8+ subset. Purified CD8+ cells from LTNP retain their ability to produce IL-2, interferon-gamma (IFN-γ) and, to a lesser degree, to produce IL-10 and IL-4. In contrast, CD8+ cells from progressors are unable to secrete IL-2 and IL-10. Although CD8+ cytokine profile does not fit with the proposed T helper (Th)1/Th2 switch in progressive HIV infection, LTNP CD8+ T cells maintain their capacity to produce IL-2 and IL-10 (Th0-like), a pattern very similar to that observed in normal HIV healthy controls. We suggest that CD8+ cells expressing CD28, CD95 and having a Th0-like profile may be considered to be associated with long-term survival. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about well differentiated B cell lymphomas.