Characterization of local memory cells in stage-classified pulmonary tuberculosis: preliminary observations.

Immunophenotype analysis and proliferative responses were investigated in bronchoalveolar lavage (BAL) cells from 21 patients with stage-classified tuberculosis: six with localized pulmonary infiltrate (LPI); seven with diffuse pulmonary infiltrate (DPI); and eight with pleural effusions (PE). Bronchoalveolar lavage cells from these patients contained a high number of cells/ml. The macrophage number was significantly lower in the DPI group (P < 0.05) compared to the LPI or PE groups. Conversely, neutrophils were markedly increased in DPI patients compared to LPI (P < 0.01) and PE (P < 0.01) patients. Lymphocyte infiltration (97.7 +/- 2.3% CD3+, > 83% alphabeta+ and CD4+ > CD8+) was observed in the three groups. A significant increase in the number of total lymphocytes (P < 0.01) and CD4+ cells (P < 0.05) was observed in the LPI group compared to the PE group. In the LPI group CD4+CD45RO+ cell infiltration was higher than CD4+CD45RA+ cells (P < 0.001), contrasting to similar numbers of these subpopulations in the DPI group. Lymphocytes from three out of three LPI patients (alphabeta+CD4+CD45RO+) responded against tuberculin purified protein derivative contrasting to the unresponsiveness of five patients with either DPI or PE. This impaired response was reverted in two out of five patients by using peripheral blood monocytes instead of alveolar macrophages. It is suggested that, in humans, alphabetaCD4+CD45RO cells are the main lymphocyte type involved in the initial local cell-mediated immune response against Mycobacterium tuberculosis.

Endemic infection with HTLV-IIB in Venezuelan Indians: molecular characterization.

The peripheral blood of 41 Yaruro and Guahibo Indians from Venezuela was examined for HTLV antibodies and DNA. Twenty-five samples (61%) were found to be infected with HTLV-IIB. The sensitivities of the serologic and DNA polymerase chain reaction (PCR) analyses were 80% and 96%, respectively. Epidemiologic studies supported both sexual and perinatal transmission of the virus. Sequence analyses of the HTLV-IIB strains from these Indians indicate that they are unique relative to HTLV-II detected in other groups of humans. HTLV-IIB-G2 isolated from a Guahibo Indian is the most divergent HTLV-IIB strain relative to the prototype HTLV-II NRA.

Highly endemic human T-lymphotropic virus type II (HTLV-II) infection in a Venezuelan Guahibo Amerindian group.

Sera from 166 Guahibo Indians (55% of the population) living in southwest Venezuela were screened by enzyme-linked immunoassay for antibodies to human T-cell lymphotropic virus (HTLV) I and II. Positive samples were confirmed by immunofluorescence and Western blot. Forty-one Guahibos (24.8%) were found to be seropositive. Polymerase chain reaction (PCR) analysis of proviral DNA in mononuclear cell lysates revealed the virus to be HTLV-II. Prevalence increased with age, and sexual contact with HTLV-II-seropositive partners was identified as a risk factor for infection. PCR amplification of a region of the pol gene, utilizing the primer pair SK110/SK111, with subsequent digestion of the 140-base-pair amplification products with HinfI and MseI restriction enzymes, showed an HTLV-II subtype-b restriction pattern in all cases. These data suggest that the substrain infecting this Guahibo community belongs to the b subtype, the most frequent among Paleo-Amerindian populations.

Lymphocyte subset diversity in idiopathic CD4+ T lymphocytopenia.

The clinical and public health importance of CD4+ T lymphocytopenia without human immunodeficiency virus infection is still unclear. We describe herein two new human immunodeficiency virus-negative patients with low numbers of peripheral CD4+ T cells and opportunistic infections (cerebral toxoplasmosis and tuberculosis plus extrapulmonary histoplasmosis). The low numbers of CD4+ CD29+ memory cells, the high percentage of gamma delta T-cell receptor cells, and the recovery of CD4+ cells after treatment were remarkable.

Decreased T-cell proliferative response to common environmental antigens could be an indicator of early human immunodeficiency virus-mediated lymphocyte lesions.

To evaluate CD4+/CD29+ cells and their responses to different antigens in polar stages of human immunodeficiency virus (HIV) infection, we studied 26 HIV-seropositive carriers (SPCs) and 15 patients with AIDS simultaneously with 20 healthy volunteers (HVs) and 10 seronegative homosexual and bisexual men (SNH). CD3, CD4, CD29, and CD45RA phenotypes were analyzed by two-color flow cytometry. Significant depletion of CD4+ T cells and both memory (CD4+/CD29+) and naive (CD4+/CD45RA+) T-cell subsets was found among SPCs and AIDS patients compared with the numbers of such cells in the HV and SNH groups. Responses to optimal doses of Candida albicans, streptokinase, and tetanus toxoid were explored in peripheral blood mononuclear cells and CD4(+)- and CD4+/CD29(+)-enriched cell populations. In SPCs, the response to C. albicans in peripheral blood mononuclear cells showed a statistically significant diminution compared with the response of HVs (15,308 versus 35,951 cpm). In addition, a significantly reduced response to streptokinase was evident only when cell preparations were CD4+/CD29+ enriched (3,048 versus 10,367 cpm). Furthermore, the SPC group comprised seven responders to at least one antigen and seven nonresponders to any of the selected specific antigens. Absence of a response in these latter patients was independent of the absolute counts of memory and naive T-cell populations. The response to tetanus toxoid, although diminished in SPCs, was not significantly different from that in controls. Our results suggest that defective responses to common environmental antigens, unrelated to the absolute number of CD4+/CD29+ cells, is probably an early indicator of an HIV-induced lymphocyte lesion.

First description of endemic HTLV-II infection among Venezuelan Amerindians.

We describe for the first time the presence of human T lymphotropic virus type II (HTLV-II) infection in Venezuela, among the Pume Amerindians living in the southern plains of the country. Antibodies to HTLV-II antigens were assessed by enzyme immunoassays (Elisa), Western blot, radioimmuno-precipitation, and immunofluorescence; titration studies against HTLV-I- and HTLV-II-infected cell lines were very useful in the differentiation of HTLV-I and HTLV-II antibodies. The HTLV-II general prevalence was 5%; however, there is a striking difference in prevalence between the truly isolated villages (0%) when compared to those living along the riverside and thus in contact with outsiders (9%). Preliminary evidence suggests sexual contact as the main source of transmission. These findings might suggest that HTLV-II in Venezuela originated through contact with outsiders rather than ancient infection related to the origins of the Pume.

Immunopathogenic aspects of infection by the human immunodeficiency virus in Venezuela.

A study of the immunopathogenic characteristics of HIV infection was begun in 1984 at the National Reference Center on Clinical Immunology (CNRIC) in Caracas, Venezuela, on 240 individuals with a variety of clinical manifestations. The most important findings were depletion of the CD4 cells in HIV-infected individuals, including asymptomatic carriers; significant reduction of the CD3-, CD16+ large granular lymphocytes (LGL) in AIDS cases; decrease in LGL cytotoxic activity in infected persons versus controls, along with increased lytic function induced by stimulation with recombinant interleukin-2 in both groups; and reduction of the CD4 population in AIDS patients, independent of the presence or absence of free serum antigen. Such research is helping to clarify the immunopathogenic mechanisms of HIV and possible geographic and demographic variations.