Production of the Th1 cytokine IFN-γ by T cells is considered crucial for immunity against Mycobacterium tuberculosis infection. We evaluated IFN-γ production in tuberculosis in the context of signaling molecules known to regulate Th1 cytokines. Two populations of patients who have active tuberculosis were identified, based on their T cell responses to the bacterium. High responder tuberculosis patients displayed significant M. tuberculosis-dependent T cell proliferation and IFN-γ production, whereas low responder tuberculosis patients displayed weak or no T cell responses to M. tuberculosis. The expression of the signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) on cells from tuberculosis patients was inversely correlated with IFN-γ production in those individuals. Moreover, patients with a nonfunctional SAP gene displayed immune responses to M. tuberculosis similar to those of high responder tuberculosis patients. In contrast to SAP, T cell expression of SLAM was directly correlated with responsiveness to M. tuberculosis Ag. Our data suggest that expression of SAP interferes with Th1 responses whereas SLAM expression contributes to Th1 cytokine responses in tuberculosis. The study further suggests that SAP and SLAM might be focal points for therapeutic modulation of T cell cytokine responses in tuberculosis.

Detailed longitudinal studies of patients with X-linked lymphoproliferative disease (XLP) may increase our understanding of the immunologic defects that contribute to the development of lymphoma and hypogammaglobulinemia in XLP. We describe progressive changes observed in immunoglobulin concentrations, lympho-cyte subsets, and Epstein-Barr virus (EBV) loads occurring in a 2-year period in a newly infected, but otherwise healthy, carrier (patient 9). We compare these findings with those observed in the patient's brother, who had hypogammaglobuline-mia and XLP (patient 4). Immunoglobulin G (IgG), IgM, and IgA concentrations increased in patient 9 during acute EBV infection, but thereafter they decreased steadily to concentrations consistent with hypogammaglobulinemia, reaching a plateau 5 months after infection. In both patients, CD19 B-lymphocyte rates remained lower than 3%, with a contraction of the B-cell memory compartment (CD27 CD19 /CD19) to 20% (normal range, 32%-56%). T-lymphocyte subpopulations showed a reduction in CD4 T-cell counts and a permanent CD8 T-cell expansion. Interestingly, CXCR3 memory T H 1 cells were expanded and CCR4 T H 2 lympho-cytes were reduced, suggesting that abnormal skewing of memory T-cell subsets might contribute to reduced antibody synthesis. Despite an expanded number of CD3 CD8 lymphocytes, increased EBV loads occurred in both patients without overt clinical symptoms of mononucleo-sis, lymphoproliferative disease, or lym-phoma.

In order to investigate hepatitis C virus (HCV) persistence and replication in peripheral blood mononuclear cells (PBMC) from a group of haemophilic individuals, HCV production and release to PBMC culture supernatants (SNs) from HCV singly infected patients and HIV/HCV co-infected patients was studied. HCV RNA + SNs were found more frequently from HIV/HCV co-infected individuals (89?5 %) with poor reconstitution of their immune status than from singly HCV-infected patients (57 %) or from HIV/HCV co-infected individuals with a good response to highly active anti-retroviral therapy (50 %). The presence of the HCV genome in culture SNs was associated with lower CD4 + T-cell counts and with a more severe clinical picture of HIV infection. In spite of prolonged negative HCV viraemia, PBMC from HIV/HCV co-infected patients released the HCV genome after culture. HCV permissive PBMC allowed generation of HCV productive B cell lines with continuous HCV replication. These findings add further weight to the involvement of PBMCs in persistence of HCV infection and emphasize the role of B lymphocytes as HCV reservoirs.

The presence of HIV-1 RNA in distal duodenal mucosa was evaluated in 44 HIV-1-positive patients. HIV-1 RNA was detected in gut tissue in antiretroviral-naive patients with high plasma viral loads, as well as in patients on HAART with plasma viral loads below the limit of detection and in patients on HAART with virological failure. The intestinal mucosa seems to serve as a reservoir poorly influenced by levels of plasma viral load or HAART.

CD4+ T follicular helper cells (TFH) were assessed in adult patients with common variable immune deficiency (CVID) classified according to the presence of granulomatous disease (GD), autoimmunity (AI), or both GD and AI (Group I) or the absence of AI and GD (Group II). TFH lymphocytes were characterized by expression of CXCR5 and PD-1. TFH were higher (in both absolute number and percentage) in Group I than in Group II CVID patients and normal controls (N). Within CXCR5+CD4+ T cells, the percentage of PD-1 (+) was higher and that of CCR7 (+) was lower in Group I than in Group II and N. The percentages of Treg and TFH reg were similar in both CVID groups and in N. TFH responded to stimulation increasing the expression of the costimulatory molecules CD40L and ICOS as did N. After submitogenic PHA+IL-2 stimulation, intracellular expression of TFH cytokines (IL-10, IL-21) was higher than N in Group I, and IL-4 was higher than N in Group II. These results suggest that TFH are functional in CVID and highlight the association of increased circulating TFH with AI and GD manifestations.