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Biomedical subjects

T Jehuda-Cohen

Publications and source records attributed to T Jehuda-Cohen.

8 recordsLinked to original sources

'Silent' HIV infection among wives of seropositive HIV carriers in the Ethiopian community in Israel.

We have previously described the phenomenon of 'silent HIV carriers', i.e. individuals with HIV specific immunity and a positive PCR for HIV-1, yet HIV seronegative. In the present study, we have looked for such 'silent' carriers among wives of individuals infected with HIV in Africa (Ethiopia). In addition to determining HIV serology, peripheral blood mononuclear cells (PBMC) were tested by PCR for HIV-1 and for their ability to generate specific antibodies to HIV upon polyclonal B-cell activation (P-BAT). Out of 16 wives so tested, three were HIV seropositive and among the 13 seronegatives, eight were P-BAT positive and five were both P-BAT and PCR positive. These findings suggest that (1) 'silent' HIV carriers may indeed be present in African populations; (2) interpretation of the 'silent' carrier phenomenon is not clear and will depend on clinical follow-up and the ability to culture virus from such carriers; and (3) results of HIV serology in this population and probably in other African populations should be viewed with caution.

Adult

Transmission of retroviral infection by transfusion of seronegative blood in nonhuman primates.

Techniques such as polyclonal B cell activation with pokeweed mitogen (PWM) and polymerase chain reaction (PCR) analysis have documented the existence of simian immunodeficiency virus (SIV)-and human immunodeficiency virus type 1-seronegative but infected humans and nonhuman primates. To establish whether blood from such seronegative but PWM- and PCR-positive monkeys can transmit infection, naive macaques were transfused with whole blood (n = 2) or cultured cells and supernatant fluid (n = 2) from two seronegative but PWM- and PCR-positive sooty mangabeys. After transfusion, three of the four recipients seroconverted, and peripheral blood mononuclear cells from all four recipients secreted SIV-reactive antibodies upon polyclonal activation in vitro and were SIV-positive by PCR that used highly specific gag primer pairs and probe. In addition, CD8+ cells from all four recipients markedly inhibited replication of SIV in autologous cells in vitro. These data suggest caution in the sole use of serologic tests for the detection of retroviral infection and document the ability of such blood samples to transmit infection.

Animals

Detection of occult simian immunodeficiency virus SIVsmm infection in asymptomatic seronegative nonhuman primates and evidence for variation in SIV gag sequence between in vivo- and in vitro-propagated virus.

Polymerase chain reaction techniques were used to identify simian immunodeficiency virus (SIV) SIVsmm gag sequences in genomic DNA isolated from peripheral blood mononuclear cells from naturally infected asymptomatic seropositive and seronegative sooty mangabeys (Cercocebus atys) and from experimentally infected but asymptomatic rhesus macaques (Macaca mulatta). The results indicate that most if not all SIV-seronegative mangabeys from the colony at the Yerkes Primate Center are in fact infected with SIVsmm despite their lack of humoral immune response, confirming previous immunological and virological observations made by our laboratory. Sequence analysis of these particular gag fragments from the mangabey revealed an average of 88% nucleotide sequence homology but 97% amino acid identity with the previously published sequence of the SIVsmmH4 clone. The significance of this finding relative to the asymptomatic state of SIV-infected mangabeys and disease-susceptible SIV-infected rhesus macaques is discussed.

Animals

Maternal transmission of SIVsmm in rhesus macaques.

Fifteen SIV-infected rhesus monkeys delivered 13 livebirths and two stillbirths; one livebirth died at three days of age. While all infants were culture-negative for SIV at birth, nine had maternal antibodies that disappeared by six months of age. Three infants subsequently seroconverted and became virus positive at 9-15 months. Milk samples from all mothers were virus-negative at parturition but samples from four animals were virus-positive at nine and 12 months. This study documents maternal transmission of SIV and suggests transmission by breast-feeding.

Animals

Polyclonal B-cell activation reveals antibodies against human immunodeficiency virus type 1 (HIV-1) in HIV-1-seronegative individuals.

Identification of human immunodeficiency virus type 1 (HIV-1)-infected individuals is of paramount importance for the control of the spread of AIDS worldwide. Currently, the vast majority of screening centers throughout the world rely on serological techniques. As such, clinically asymptomatic but HIV-infected, seronegative individuals are rarely identified. In this report we show that 18% (30/165) of seronegative individuals who were considered to be a unique cohort of patients at high risk for HIV infection had circulating B cells that, upon in vitro polyclonal activation with pokeweed mitogen, produced antibodies reactive with HIV. Furthermore, polymerase chain reaction analysis of DNA obtained from aliquots of the peripheral blood mononuclear cells from these seronegative but pokeweed mitogen assay-positive individuals tested revealed the presence of HIV-specific sequences in a significant number of samples. In addition, depletion of CD8+ T cells from peripheral blood mononuclear cells of HIV-1-seronegative individuals prior to in vitro culture with pokeweed mitogen resulted in increased sensitivity for detecting HIV-reactive antibodies. This assay has obvious epidemiological implications, especially in the case of high-risk groups, and also provides a simple technique to enhance detection of HIV-infected individuals. Of further interest is the determination of the mechanisms related to the lack of HIV-specific antibodies in the serum of these infected individuals.

Antigens, Differentiation, T-Lymphocyte

Does stem cell self renewal and progenitor cell commitment operate through an effector-memory cell mechanism?

We propose a model for stem cell self renewal and transition into commitment towards a variety of cell lineages. In this model the production of both "effector cells" (as represented by the mature cells in the different cell lineages) and of progenitor "memory" lymphocytes, takes place concomitantly. The experimental evidence supporting this model is as follows: Pure lymphocytic suspensions (PLS) are established and persist in culture when nude mouse-spleen and lymph-node cells are maintained on X-irradiated fibroblast monolayers in the presence of the S-phase cytotoxic agent cytosine arabinoside (Ara-C). From these PLS the following colony types can be initiated by the corresponding inducing (stimulating) factors (CSF): histiocytes (tissue macrophages) - CSF-1; granulocytes-macrophages (GM) - CSF-GM; mast cells - MMSF; granular-NK mucus secreting cells - IL-2; and multilineage colonies - IL-3. Mitotically active blast cells (formed by transformation of lymphocytes), condense into motile small cells when the stimulatory factor is removed. These "memory" lymphocytes are committed as they carry the receptors for the specific CSF; they respond by retransformation into blast cells. A dramatic increase in mast-cell colony forming cells is found in bone marrow, spleen and lymph-nodes of mice infected with Schistosoma mansoni. By maintaining PLS with both Ara-C and each of the CSFs and then titrating the incidence of CFC in the residual PLS, we find that each one of the CSFs acts on an independent set of cells in the PLS to produce the corresponding colony type. Finally, the concept suggests that the various blast cells carrying the receptors, undergo condensation into memory lymphocytes when dissociated from the environment prevailed by the corresponding CSF. In this way pluripotential blast-cells condense into motile lymphocytes which are committed to pluripotentiality.

Animals