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PubMed1979

DRw antisera react with activated T cells.

Nylon wool-purified T cells appear to be nonreactive in a lymphocytotoxicity assay with HLA-DRw antisera and complement before cell activation. However, after activation in mixed lymphocyte culture, responder cells express determinants that are strongly reactive with DRw alloantisera after 6 days and gradually disappear by 16 to 18 days. Restimulation of the primed cells resulted in re-expression of the blast determinants. Mitogenic stimulation with Con A or purified PHA (HA-17) also resulted in temporary expression of these determinants; reactivity usually conformed to DRw genetic restriction; however, occasional extra reactions occurred that were variable depending on the method of activation (i.e., MLC, Con A, or HA-17). The results suggest the presence of additional allospecificities within some of the DRw antisera that react with "Ia-like" antigens on activated cells from unique subsets of T cells. Whether these DRw antisera contain antibodies against T cells or agains activation or differentiation T cell antigens is not as yet clear.

Adult↗
PubMed1979

Surface properties and in vitro functional capacities of human T lymphocyte subsets separated by linear density gradients.

Human lymphocytes derived from various central and peripheral sources were separated on linear density gradients (LDG). Cells from individual density fractions were tested in parallel for: the capacity to form nonimmune rosettes with neuraminidase-treated SRBC, the number of surface-associated HTLA, and in vitro proliferative responses to mitogenic lectins and alloantigens. Heterogeneous density distribution profiles were obtained for all sources of human T cells and revealed an organ specificity. The various T cell density classes obtained from identical organs as well as the identical density classes of different sources revealed to some extent differences in their surface marker patterns and/or their in vitro reactivities. On the basis of the combined techniques at least two major subsets among thymocytes were identified that differed in both surface properties and functional capacities. Density classes of T cells from all peripheral sources were distinguished from thymocytes by a homogeneous lowered HTLA expression. Whereas clear-cut differences in the in vitro functional capacity were observed between the two thymocyte subsets, less striking but still significant differences were found to exist among the various density classes of peripheral T cells.

Animals↗
PubMed1977

Ultrastructural, cytochemical, and membrane surface marker characteristics of the atypical lymphocytes in infectious mononucleosis.

Atypical lymphocytes from nine young adults with acute infectious mononucleosis (IM) were studied for morphologic, ultrastructural, cytochemical, and membrane surface marker characteristics. There was an absolute increase in T lymphocytes in the patients. Atypical lymphocytes accounted for 83%-96% of the lymphocyte population. These lymphocytes contained cytoplasmic inclusions which ranged in size from 1000 to 6000 A, were usually membrane bound, and consisted of parallel arrays of microtubulelike structures. The inclusions, which have been referred to as parallel tubular arrays (PTA), were found in 15%-75% of the lymphocytes from the IM patients. Ultrastructural cytochemical methods demonstrated acid phosphatase activity within many of the membrane-bound PTA. The function of the PTA is unknown. Since they were observed only in the lymphocytes which appeared to correspond to the atypical lymphocytes on light microscopy, the majority of which typed as T cells, there appears to be an association between PTA and T lymphocytes. It is possible that PTA identify a specific subset of T lymphocytes which is expanded in IM. Alternatively, PTA may be a transient finding in lymphocytes appearing only in certain biologic states of the cell such as during T-lymphocyte activation.

Acid Phosphatase↗
PubMed1978

Functional differentiation of B lymphocytes in agammaglobulinemia. III. Characterization of spontaneous suppressor cell activity.

The addition of fresh peripheral blood mononuclear cells (PBL) from four of seven patients with agammaglobulinemia to generated hemolytic plaque-forming cells (PFC) resulted in a dose-dependent suppression of PFC. This spontaneous suppressor cell activity (SSA) was restricted to the four patients who could generate a PFC response in vitro. SSA was mediated by a small subset of E-rosetting T lymphocytes characterized by theophylline-sensitive E-receptors and surface receptors for Fc-IgG. The effects of SSA were temperature dependent and reversible, and pokeweed mitogen could prevent the rapid decline of SSA observed during culture. Augmentation of SSA was achieved by agents known to increase intracellular levels of cyclic AMP, whereas lithium chloride abrogated SSA, including the drug-induced effects. Cells mediating SSA may play a role in preventing the normal transition of pre-B cells to B cells in patients with agammaglobulinemia without B lymphocytes.

Agammaglobulinemia↗
PubMedDate not supplied

Surface markers and functional characteristics of human blood lymphocytes residing in the operational "null" subset.

After removal of nylon wool-adherent B and E rosetting T cells from the human blood lymphocyte population, a small fraction remains, often denoted as "null" subset. This fraction contains lymphocytes which are highly efficient in antibody-dependent and non-selective lymphocyte cytotoxicity. These cells possess markers. About half of them carry Fc receptors, and the majority has low avidity E and C3 receptors. Removal of low avidity E receptor-carrying cells did not abolish cytotoxicity to K-562 cells. The majority of cells carry receptors for Epstein-Barr virus but cannot be infected. The cells in mixed lymphocyte culture have a low reactivity. They aare stimulated by PHA and ConA to a similar extent and differ from the cells which readily sediment as E rosettes: these respond stronger to PHA. The "null" fraction may contain stem cells common for both T and B lineages.

Animals↗
PubMed1977

Mouse red cell rosette formation by subpopulations of human lymphocytes.

In six separate experiments, 7-2% of purified peripheral blood lymphocytes from normal donors were shown to form rosettes with mouse erythrocytes. Normal T and B lymphocytes were separated according to their membrane properties, by E-rosette formation or fractionation on anti F (ab')2 column. The results obtained in both the separation procedures used were in good agreement: T lymphocytes were never found to form mouse red cell rosettes. On the contrary, enrichment of suspensions in B lymphocytes resulted in an increased percentage of mouse red-cell rosette-forming cells. Under the technical condition used, peroxidase-positive monocytes were not shown to form such rosettes. However, if all the mouse red cell rosette-forming cells were shown to be of B nature, not all the B lymphocytes form rosettes with mouse erythrocytes and it is not unlikely that this marker could be characteristic for a subset of Ig-bearing B lymphocytes.

Animals↗
PubMed1977

The role of macrophages in the generation of T helper cells. V. Evidence for differential activation of short-lived T1 and long-lived T2 lymphocytes by the macrophage factors GRF and NMF.

The generation of T helper cells in vitro requires macrophages or macrophage-derived factors such as genetically related macrophage factor (GRF) or nonspecific macrophage factor (NMF). However, there is a basic difference of T helper cell induction when using particulate antigens. The present study demonstrates that this difference is based on the activation of two different T cell subsets. GRF activates short-lived 'T1' cells which amplify the induction of T2 cells, which are the helper cell precursors. Thus, the genetic restriction of T helper cell induction seen with soluble antigen or GRF lies on the level of macrophage or GRF interaction with T1 cells. NMF (or macrophages) and particulate antigens directly activate the helper cell precursor (T2) indicating no requirement for T1-T2 cooperation. The direct activation of the helper cell precursor with particulate antigens does not require histocompatible macrophages or NMF from histocompatible macrophages. The present results may explain some of the discrepancies reported in the literature concerning the genetic requirements and specificity of T cell activation.

Animals↗
PubMed1977

Heterogeneity of B cells reacting with T-cell factors. Evidence for matching T-cell and B-cell subsets.

Spleen T cells have been stimulated with Concanavalin A (Con A) under conditions which lead to the production of non-specific factor (NSF), a substance which replaces T cells for B-cell responses to certain antigens. We have examined the ability of multiple aliquots of B cells to react to the NSF derived from single T cells, and have found great heterogeneity of response. We postulate that there exist subsets of T cells which vary in either the quantity or the quality of the non-specific factor(s) they can produce on stimulation, and that in turn there must also be matching subsets of B cells which may vary in their susceptibility to such factors.

Animals↗
PubMed1977

Human T lymphocyte subset identification according to avidity for sheep erythrocytes and rosetting capacity with allogeneic red blood cells.

Peripheral blood T lymphocytes of healthy adults were separated in appropriate Ficoll-Hypaque mixtures according to their avidity for sheep red blood cells (SRBC) and re-rosetted with both SRBC and human red blood cells (HRBC). The results showed that separation procedures causing relative depletion of lymphocytes with high avidity for SRBC led to a parallel increase in the percentage of cells forming rosettes with HRBC. Separation procedures leading to almost complete depletion of cells forming rosettes with SRBC also almost completely eliminated cells forming rosettes with HRBC. The overall data suggest that circulating T cells of healthy adults can be divided into two subsets according to their avidity for SRBC. T lymphocytes with low avidity for SRBC preferentially express receptors for HRBC. These data are presented as further evidence of T lymphocyte heterogeneity.

Animals↗
PubMed1977

Neuraminidase- and trypsin-induced exposure to membrane receptors for IgG and IgM molecules on human peripheral blood lymphocytes.

Brief incubation of human peripheral blood lymphocytes with vibrio cholerae neuraminidase (VCN) or trypsin revealed hidden membrane receptors for IgG and IgM molecules. The hidden receptors were found on T lymphocytes as shown by double-label and mixed rosetting experiments and by studies of T-enriched populations. Although IgM receptors were undetectable on freshly isolated lymphocytes, a mean of 17.1% of VCN-treated lymphocytes rosetted with ox erythrocytes coated with IgM antibody (EA-IgM). Prior to trypsin treatment a mean of 14.6% of human T lymphocytes rosetted with ox red cells coated with IgG antibody (EA-IgG). After incubation with trypsin this figure increased significantly (P less than 0.005) to 44.5%. VCN-treatment also significantly increased (P less than 0.005) the mean percentage of EA-IgG rosette-forming T cells to 38.5%. The T-cell receptor for IgG was shown to be trypsin-resistant while the IgM receptor was shown to be trypsin-sensitive. Using mixed rosettes, a tentative T-cell subset was identified which expressed both IgG and IgM membrane receptors. Also, a minor subset with IgM receptors alone and a larger subset with only IgG receptors were identified.

Binding Sites, Antibody↗
PubMed1978

Subpopulations of splenic T cells regulating an antihapten antibody response. I. Helper and amplifier cells.

There was a pronounced quantitative difference between the helper activities of B6C3F1 splenic T cells sensitized with unmodified vs modified antigens of SRBC. Modified SRBC induced the greater helper activity which was measured by the magnitude of an anti-TNP response (IgM and IgG) elicited in vivo by virgin B lymphocytes. Antigen modification was produced by conjugating SRBC with the hapten or simply by incubating SRBC in cacodylate buffer. There were restrictions with respect to both erythrocyte species and mouse strains for this differential priming to occur. The relatively poor performance of SRBC-primed T lymphocytes was apparently not due to suppressor T cells, but rather to activation of only one of two identified T cell subpopulations required for full helper activity. Unmodified SRBC activated a subpopulation of "helper" cells characterized as sensitive to elimination by ATS and long-lived after ATx, but failed to activate in B6C3F1 mice a second subpopulation of "amplifier" cells resistant to elimination by ATS and short-lived after ATx. In contrast, modified SRBC activated both helper and amplifier cells. Under appropriate conditions these subsets of T cells were strongly synergistic in promoting antihapten antibody formation especially of the IgG class. The involvement of two distinct types of T lymphocytes in the positive regulation of antibody responses raises interesting and novel questions concerning the sequence of events in the triggering of B cells and the subsequent development of the response.

Animals↗
PubMed1979

Local xenogeneic graft-vs-host reaction: a practical assessment of T cell function among cancer patients.

The local xenogeneic graft-vs-host reaction (XGVHR) was used as a practical bioassay to assess T lymphocyte function and immunocompetence among cancer patients. Positive XGVHR was found in 99.5% of normal donors, 70% of cancer patients with early stage disease, and 30% of cancer patients with metastatic disease (p less than 0.001). A minimum of 4.5 x 10(6) immunocompetent T lymphocytes are necessary in order to elicit a positive XGVHR. Negative reactions among cancer patients are characterized by the lack of edema fluid accumulation and the appearance of the most basophils at the test site. This suggests that insufficient amounts of lymphokines are being released by the incompetent T lymphocytes, whereas the host is capable of mounting a rejection reaction as evidenced by the appearance of the basophils. Preliminary evidence suggests that the immunologic defect detected by the XGVHR cannot be corrected by monocyte depletion. The identification of putative suppressor T cell subsets may bear immunotherapeutic implications in the future.

Animals↗
PubMed1975

Casein-induced experimental amyloidosis. V. The response of lymphoid organs to T and B mitogens.

Functional and morphologic studies were performed on the lymphoid organs of inbred CBA/J mice receiving chronic casein administration. In the spleen, this regimen produces marked reticuloendothelial proliferation between 8 and 16 injections (preamyloid phase) and amyloid deposition between 16 and 24 injections. No amyloid was found in the thymus, lymph nodes, and bone marrow of these animals. Phytohemagglutinin and concanavalin A lymphocyte responses as measured by 3-H-thymidine incorporation were reduced in the spleen and lymph node of preamyloid animals but demonstrated partial recovery during the amyloid phase. Phytohemagglutinin and concanavalin A stimulation of thymic cells was significantly increased during both stages of amyloid induction, although the histologic studies revealed a marked involution of the thymic cortex. Lipopolysaccharide stimulation of spleen cells was normal in preamyloid and amyloid animals whereas in lymph node and bone marrow lipopolysaccharide responses were significantly decreased. The findings suggest a selective removal of subsets of T cell populations in the spleen and thymus and migration of B cells from bone marrow to the spleen during experimental amyloidosis.

Amyloidosis↗
PubMed1976

Immunological activities of rat lymphocytes. I. Mitogenic responses and surface markers of lymphocytes from normal, thymectomized and B rats.

Lymphocytes from the peripheral blood, thoracic duct, spleen and lymph nodes of normal, thymectomized (TX) and thymectomized lethally irradiated marrow reconstituted (TXBM or B rats) Lewis rats were studied for their ability to proliferate in vitro in the presence of Con A or PHA. At the same time the lymphoid tissues of these animals were examined for the presence of B cells or T cells by immunofluorescence staining with antiserums to rat immunoglobulins or rat brain antigens (ARBS), respectively. The specificity of ARBS fort T cells was first established in both cytotoxicity and immunofluoresecnce studies with thymocytes as well as pruified T and B cells. In various lymphoid tissues from TX and B rats, cells carrying brain antigens were found which were unable to respond to Con A and PHA. Thymectomy has a lesser effect on the response to Con A that to PHA; this was particularly true in the thoracic duct where, following thymectomy, lymphocytes continued to respond to Con A but lost their ability to respond to PHA. This suggests that the response to PHA and Con A may belong to different cells' subsets but that the ability to respond to either one of these mitogens may be impaired in cells carrying known T cell markers.

Animals↗
PubMed1977

Ala-1: murine alloantigen of activated lymphocytes. II. T and B effector cells express ala-1.

Ala-1 (activated lymphocyte antigen-1) is a murine alloantigen expressed only on activated peripheral T and B lymphocytes. The presence or absence of Ala-1 on specific functional lymphocyte subsets was determined by treating the relevant cell population with anti-Ala-1 and complement, and assaying for residual functional activity. By this method, Ala-1 was shown to be on in vivo primed killer T cells cytotoxic for allogeneic tumor cells. It was also found on helper T cells generated in vivo to sheep red blood cells, and on IgM and IgG plaque-forming cells (PFC) to sheep red blood cells. In contrast, splenic precursors of helper cells and of IgM PFC to sheep red blood cells were completely resistant to treatment with anti-Ala-1 and complement. These findings indicate that effector cells can be distinguished from their nonactivated precursors by their expression of Ala-1.

Animals↗
PubMed1978

Adherent cell function in murine T lymphocyte antigen recognition. II. Definition of genetically restricted and nonrestricted macrophage functions in T cell proliferation.

The mechanisms by which adherent cells, presumably of mononuclear phagocytic lineage, influence in vitro antigen-specific activation of murine T lymphocytes was examined. Two distinct functions for macrophages could be discerned. One macrophage function is dependent on a soluble factor produced by cultured adherent cells and is most easily studied with complex multideterminant antigens. This factor is neither antigen-specific nor MHC-restricted in its action in that PEC, regardless of haplotype, produce factor in the absence of antigen. A second function, antigen-specific T cell activation, is seen when antigens of more restricted heterogeneity are used, such as those under the control of Ir genes. This latter activity demands identity or partial identity between the antigen-presenting cell and the primed T cell, thus suggesting an additional specific, genetically restricted function for macrophages in in vitro antigen recognition. Whether these adherent cell functions are mediated by all or distinct subsets of cells was not established.

Animals↗