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Biomedical subjects

E C DeFreitas

Publications and source records attributed to E C DeFreitas.

9 recordsLinked to original sources

Regulation of interleukin 2 receptors on T cells from multiple sclerosis patients.

Receptors for interleukin 2 (IL-2) are absent on resting T lymphocytes and are induced by antigenic and mitogenic stimulation. After a limited time (8-12 days), these receptors on normal T cells are down-regulated despite the presence of receptor-saturating concentrations of IL-2. We report here that both antigen- and mitogen-induced T-cell lines and clones obtained from peripheral blood and cerebrospinal fluid of multiple sclerosis patients show prolonged expression of IL-2 receptors. This expression is coincident with a prolonged responsiveness to the proliferative effects of IL-2. In addition, Leu 3+, IL-2 receptor-positive T-cell clone from the cerebrospinal fluid of a multiple sclerosis patient has been established and maintained for more than 1 year without IL-2. This clone has some morphologic and histochemical properties of T cells transformed or infected by human T-lymphotropic virus type I.

Antibodies, Monoclonal↗

Human T-lymphocyte response in vitro to synthetic peptides of herpes simplex virus glycoprotein D.

Immunization of mice with a synthetic peptide that corresponds to a murine antibody-defined immunodominant domain of herpes simplex virus (HSV) glycoprotein D (gD) induced neutralizing antibodies against HSV types 1 and 2 and protected animals against a lethal challenge with HSV type 2 (Dietzschold, B., Eisenberg, R., Ponce de Leon, M., Golub, E., Hudecz, F., Varicchio, A. & Cohen, G. (1984) J. Virol. 52, 431-435). We report here that human peripheral blood T cells from HSV-seropositive and -seronegative adult donors are activated by this synthetic peptide in vitro. Interleukin-2-dependent T-cell lines established from these cultures respond specifically to peptides containing residues 1-23 of HSV gD and to a panel of overlapping peptides within this domain. The T-cell proliferative response was maximal when the majority of interleukin-2-propagated T cells were of the helper phenotype and the peptides were at least 16 amino acids long. Peptides of 8 or 12 amino acids from the carboxyl terminus were nonstimulatory. Peptide-activated T-cell lines from sero-negative donors less than 11 years old could be established in vitro, but most cells were of the suppressor/cytotoxic phenotype and demonstrated no antigen-specificity when tested with the panel of synthetic peptides.

Amino Acid Sequence↗

Human antigen-specific T hybridomas.

Production of antigen-specific hybridomas has been achieved by fusion of HGPRT-negative mutant of Jurkat and antigen-specific TH cell lines. Selection of clones for specificity was best accomplished by the binding of radiolabeled hybrid clones to antigen-pulsed monolayers. Functional lymphokines such as IL-2 and BCGF were induced by antigenic stimulation in the presence of AC. AC function of EBV-transformed autologous B cells was as efficient on a per cell basis as autologous monocytes. Loss of specificity and function was observed in the first 5-6 months of culture which was coincident with chromosome loss. Recovery of specific functional hybrids was accomplished by repeated subcloning during this period. After this time, hybrids have maintained function for at least one year. This methodology allows the study of certain T cell functions without the requirement of periodic restimulation with autologous monocytes. Since EBV-B cell lines can serve as AC to induce lymphokines, large quantities of material can be prepared for biochemical studies.

Antibodies, Monoclonal↗

In vitro propagation of antigen-specific T lymphocytes that adoptively transfer resistance to Listeria monocytogenes.

Murine T cells generated against heat-killed Listeria monocytogenes or Listeria intracellular product (LIP) were propagated in a source of Interleukin 2. Both T-cell cultures were greater than 98% Lyt 1+, 2/3- and proliferated specifically against LIP and L. monocytogenes crude whole-cell antigen in vitro. Proliferation of both T-cell cultures required the presence of antigen and accessory cells syngeneic to the T cells at the left end of the major histocompatibility complex. The ability of these cultures to adoptively transfer protection against challenge with viable Listeria cells was dramatically different. As few as 10(6) LIP-specific T cells conferred significant protection against a lethal challenge of Listeria cells, whereas cultures induced against crude whole-cell antigen showed little or no protective function. The resistance conferred by LIP-specific T cells was specific in that the cells did not reduce the mortality seen after challenge with Salmonella typhimurium.

Animals↗

Macrophage-dependent activation of antigen-specific T cells requires antigen and a soluble monokine.

Antigen-induced T cell proliferation requires T cell interaction with antigen in the context of MHC I region-compatible accessory cells. The resulting activation and proliferation of T cells involves the production and utilization of several lymphokines or interleukins. This report describes experiments wherein these events could be separated into two phases, T cell activation and T cell proliferation. The first phase was achieved by stimulating antigen-specific T cell lines with antigen-pulsed ultraviolet light-irradiated accessory cells. T cell proliferation (second phase) could then be initiated by the addition of a soluble lymphokine with the characteristics of interleukin 1 (IL 1). These effects were only observed with homologous antigen and accessory cells syngeneic to the T cells at the I-A and E/C subregion of the MHC. This report has two applications in the study of lymphocyte-lymphokine interactions. First, T cell recognition of antigen and antigen-induced T cell proliferation can be examined as physically separate events. Secondly, this system may be used as a specific and sensitive means of measuring the effects of IL 1 on T cells.

Animals↗

Antigen-specific human T-cell hybridomas with helper activity.

Human T cell hybridomas were produced by fusing the hypoxanthine phosphoribosyltransferase-deficient line of the human T cell lymphoma Jurkat with a continuous line of normal human T cells specific for tetanus toxoid (TeT). The hybridomas were selected for their ability to produce interleukin 2 after exposure to TeT on semiautologous monocytes and for their ability to bind to TeT-pulsed semiautologous monocytes. These antigen-specific T hybridomas demonstrated potent helper activity for semiautologous B cells as determined by the production of high levels of anti-TeT antibody in vitro.

Antibody Formation↗

Multiple sclerosis and human T-cell lymphotropic retroviruses.

A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

Adolescent↗

Tropical neuromyelopathies and retroviruses: a review.

Debilitating disorders of the nervous system have a relatively high prevalence in the tropics, a geographic region that is often deficient in specialists in the fields of neurology and epidemiology. During World War II, attention was called to a possible nutritional origin for most of these diseases. Recently, however, human T lymphotropic virus type I (HTLV-I), formerly linked only to a rare form of leukemia (adult T cell leukemia), has been associated with a spastic paraplegia observed mostly in tropical areas and referred to as tropical spastic paraparesis. This entity is also observed in nontropical areas endemic for HTLV-I, including Japan, South America, and the southern United States. Viruses of the HTLV family are being associated increasingly with pathology in humans. The pathogenesis of HTLV-I-associated tropical spastic paraparesis remains to be understood. However, future research is expected to favor a multidisciplinary approach, with exciting potential insights derived from the fields of neurology, immunology, and infectious diseases. The aim of this review is to summarize contemporary research related to the viral etiology of this clinical entity.

Acute Disease↗