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H S Micklem

Publications and source records attributed to H S Micklem.

At least 37 records · Page 2Linked to original sources
PubMed1983

Circadian variation of lymphocyte subpopulations: a study with monoclonal antibodies.

Use of monoclonal antibodies to identify subpopulations of circulating lymphocytes in healthy adults showed pronounced circadian variations in total T cells, the two major T cell subsets, and HLA-DR+ lymphocytes. When the results for the T cell subsets were expressed as a ratio (helper:suppressor) no significant rhythmic variation was observed. Lymphocytes bearing a surface antigen identified by the HNK-1 antibody (a population containing the natural killer and antibody dependent killer activity) did not show significant rhythmic variation. There was an inverse relation between plasma cortisol concentration and numbers of T and B cells. These observations have therapeutic implications and should be considered in the course of immunological monitoring.

Adult↗
PubMed1983

The distribution and possible significance of cells identified in human lymphoid tissue by the monoclonal antibody HNK-1.

The monoclonal antibody HNK-1 identifies a subpopulation of lymphocytes containing almost all of the natural killer (NK) and antibody-dependent killer (K) cell activity. Using an immunoperoxidase technique on frozen tissue sections of human spleen, tonsil and lymph node we have demonstrated that cells identified by this antibody are almost exclusively confined to germinal centres. Comparison with the distribution of B cells, T cells and T cell subsets underlines the distinctive distribution of these cells for which a physiological role in the maturation of antibody affinity during immune responses is suggested.

Antibodies, Monoclonal↗
PubMed1982

Clonal interaction in tumours.

The development of cancer is contingent on the emergence of at least one clone of transformed cells. One method used to investigate whether human tumours are monoclonal depends on the mosaicism in the normal tissues of women heterozygous for the two forms of the enzyme glucose-6-phosphate dehydrogenase (G-6-PD). This mosaicism results from the inactivation of one X chromosome in all somatic cells and should not exist in a monoclonal population. Following the discovery in feral mice of an electrophoretic variant (A) of the X-coded enzyme phosphoglycerate kinase (PGK-1) which differs from the form (B) found in common laboratory mouse strains it was reported that fibrosarcomas induced chemically in hybrids of feral and laboratory-bred mice expressed both enzyme phenotypes, but the conclusion that both were expressed by neoplastic cells was based solely on morphological evidence. The development of histocompatible substrains of mice homozygous for one or other alloenzyme has made it possible to study the clonal composition of tumours under experimental conditions in which the neoplastic status of subpopulations of cells can be verified by transplantation. The experiments we now report, while confirming that murine fibrosarcomas are often pleoclonal, show that the clonal composition may change markedly during tissue culture and on transplantation to congenic hosts. These changes presumably reflect changes in the growth kinetics of differentiating subpopulations of the tumour. Cloned sublines are less readily transplantable than uncloned tumour cell populations, and some sublines are less readily transplantable than others; this suggests that sublines resistant to a host's attack are selected on transplantation or that some sublines require the cooperation of others to survive. We postulate that changes in clonal composition occur also during tumour development, metastasis and recurrence.

Animals↗
PubMed1982

Serial depletion and regeneration of the murine hematopoietic system. Implications for hematopoietic organization and the study of cellular aging.

The mouse hematopoietic system was subjected to repeated depletion and regeneration either by serial transfer of bone marrow cells through lethally irradiated recipients or by repeated treatment with the cycle-active drug hydroxyurea (HU). The capacity of surviving stem cells to proliferate and self-renew was assayed at intervals by two methods: (a) the spleen colony method; and (b) competitive repopulation of irradiated recipients using chromosome markers, with normal bone marrow cells as an internal control. The progressive decline in stem cell function that occurred during serial transfer of bone marrow and that had already begun after a single transfer was not seen during HU treatment; up to 25 pairs of HU injections given over more than 1 yr had no discernible effect on the number of stem cells present 3 wk after the final injection or on their capacity to self-renew. Within 2 d after exposure to HU, the average self-renewal capacity of surviving stem cells was enhanced. This implies that the drug selectively eliminates poorly self-renewing stem cells and hence that these enter cycle more readily than stem cells with a high self-replicative potential. However, the fact of being in cycle at the time of injection did not of itself affect self-renewal. The results show that serial transfer of bone marrow is not a valid method for studying clonal aging phenomena because it does not fulfill the assumptions on which such studies are based. No evidence was obtained for any intrinsic limitation in the capacity of bone marrow populations for repeated regeneration after HU-induced depletion. However, this does not necessarily imply that individual hematopoietic clones are capable of indefinite expansion because hematopoiesis may (as suggested by the relative resistance of highly self-replicative stem cells to mitogenic signals) proceed on the basis of clonal succession.

Animals↗
PubMed1982

Special proliferative sites are not needed for seeding and proliferation of transfused bone marrow cells in normal syngeneic mice.

The widely held view that transfused bone marrow cells will not proliferate in normal mice, not exposed to irradiation or other forms of bone marrow ablation, was reinvestigated. Forty million bone marrow cells from male donors were given to female recipients on each of 5 consecutive days, 5 to 10 times the number customarily used in the past. When the recipients were examined 2-13 weeks after the last transfusion, donor cells were found to average 16-25% of total marrow cells. Similar percentages of donor cells were found when variants of the enzyme phosphoglycerate kinase determined electrophoretically were used for identification of donor and recipient cells. Evidence is presented that the proportion of donor cells is compatible with a linear dependence on the number of cells transfused over the range tested--i.e., 20-200 million bone marrow cells injected intravenously. Special proliferative sites thus do not appear to be required.

Animals↗
PubMed1982

[Cell aging].

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Animals↗
PubMed1981

T cell ontogeny. Organ location of maturing populations as defined by surface antigen markers is similar in neonates and adults.

Earlier studies have suggested that splenic T cell populations in nursling mice (less than 18 d of age) have Lyt cell surface antigens that identify them as less mature than their adult counterparts. Studies presented here, however, demonstrate that the expression of the Thy-1, Lyt-1, Lyt-2, and Lyt-3 T cell antigens is virtually identical in 14-d-old and adult T cell populations even though at 14 d, T cells constitute less than 10% of the total spleen cell population. Because the expression of these antigens on the immature (cortical) thymocyte population differs substantially from their expression on peripheral T cells, the maturity of splenic T cells as judged by these criteria is similar in nurslings and adults. Very few cells in the neonatal thymus 4 h after birth correspond, in terms of antigen expression, to the more mature (medullary) thymocyte population of adults, but such cells develop rapidly during the first few days of life. They are present, therefore, sufficiently early to serve as the immediate source of peripheral T cells, as they apparently do in the adult. This then suggests that the locations for the major T cell maturational events are established within the first 2 wk of life of the mouse and maintained as such thereafter. The use of monoclonal antibodies and quantitative immunofluorescence analysis in our studies probably explains the differences between our findings and those reported previously, which relied on cytotoxic depletion by alloantisera and complement to estimate the frequencies of cells carrying the Lyt differentiation antigens in nurslings.

Aging↗
PubMed1981

Immunodepression of thymus-independent response to dextran in mouse malaria.

The thymus-independent antibody response to the alpha 1-6 epitope of dextran B512 was depressed strongly during acute non-lethal Plasmodium yoelii yoelii malaria, but not during low-grade chronic Plasmodium berghei infection. In the acute infection, which is self-limiting, the duration of severe immunodepression was short and was seen only in mice immunized at or around the time of peak parasitaemia. Mice primed at this time responded normally to challenge 20 days later: thus the primary exposure to dextran had no apparent tolerogenic effect. Spleen cells from the immunodepressed mice responded well after transfer to non-infected irradiated hosts, and did not interfere with the adoptive response of normal cells; this, and the fact that P. y. yoelii induced immunodepression in T cell-deprived mice, suggested that T suppressors were not involved. Lack of accessory function, and possibly active suppression, by macrophages remain the most probable explanation for the effect of malaria infection on T-independent antibody responses.

Animals↗
PubMed1980

T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views.

Using monoclonal antibodies and multiparameter fluorescence analyses, we show that the expression of Lyt-1, Lyt-2, and Lyt-3 on T cell subpopulations is more complex than was originally recognized by the cytotoxic depletion studies with conventional reagents that defined the Lyt-1+2+3+, Lyt-1+2-3-, and Lyt-1-2+3+ populations. We detect at least some Lyt-1 on all T (Thy-1-bearing) lymphocytes; however, in agreement with previous studies, we find that Lyt-2+3+ cells are more difficult to depelete with anti-Lyt-1 than Lyt-1+2-3- cells. Surprisingly, we found a small subpopulation of cells carrying relatively large amounts of Lyt-1 and no Thy-1 detectable by fluorescence-activated cell sorter analysis. We also detect cells with this phenotype histologically in B cell zones (primary follicles) and germinal centers in spleen and lymph nodes. In general, the Lyt-1 only population represents approximately 2% of spleen cells. The relative quantitative expression of Thy-1, Lyt-1, Lyt-2, and Lyt-3 changes systematically during T cell maturation. Among Lyt-1+2+3+ cells in the thymus, Thy-1 and Lyt-2 are high, whereas Lyt-1 is low. Among splenic T cells, in contrast, Thy-1 is low, Lyt-1 is high, and Lyt-2 and Lyt-3 are a little higher than in thymus. In general, Thy-1 expression is negatively correlated with Lyt-1. Thus, even among splenic and lymph node T cells subpopulations exist that tend to be either high Thy-1 and low Lyt-1 or vice versa. Lyt-2+3+ cells represent approximately 85% of thymocytes but only approximately 35% of splenic or lymph node T cells. The Lyt-2+3+ cells are found predominantly in the low Lyt-1, high Thy-1 subpopulation.

Animals↗
PubMed1980

Age-related changes in cell localization and proliferation in lymph nodes and spleen after antigenic stimulation.

Antigen-dependent localization of 51Cr-labelled lymphocytes, and the subsequent uptake of IUdR into lymphoid organs has been studied as a function of age. Measures of cell localization indicated that while old age can alter the patterns of entry of lymphocytes into lymph nodes and spleen, these changes are variable and probably not sufficient alone to explain decreased primary antibody responses in old animals. Proliferation of cells, however, was consistently affected in both organs and this phenomenon is discussed in terms of abnormal T-cell function.

Aging↗
PubMed1979

Immunosuppression in murine malaria. IV. The secondary response to bovine serum albumin.

The anamnestic antibody response of CBA mice to bovine serum albumin was characterized by a rapid production of high-avidity antibody. After 3 weeks both the total amount of antibody and its avidity declined but still remained above those seen in the primary response for at least 6 weeks. The effects of acute Plasmodium berghei and Plasmodium yoelii yoelii infections upon the induction and the expression of this anamnestic response were studied. Mice infected with these malaria parasites responded poorly to primary immunization and the immunological memory generated was quantitatively subnormal. In addition, presence of the infection during a period between approximately the second and third weeks of the primary response prejudiced the development of high-avidity memory. Optimally primed mice, challenged during a subsequent acute infection, responded well initially, but were unable to maintain the secondary response at a normal level in terms of both quantity and avidity of the antibody. However, if challenge was delayed until after recovery from the infection, a normal secondary response ensued. Antibody concentrations in the sera of primed animals declined rapidly during infection. This was at least partly due to increased catabolism.

Acute Disease↗
PubMed1979

Immunosuppression in murine malaria. III. Induction of tolerance and of immunological memory by soluble bovine serum albumin.

The primary antibody response to alumadsorbed BSA was depressed when initiated during low-grade chronic Plasmodium berghei malaria in mice, as previously reported during acute P.y. yoelii infection. Induction of immunological memory by soluble polymerized BSA was abolished in both infections; in infected hosts this normally immunogenic stimulus resulted in partial tolerance. In contrast to the depression of immune response, neither infection interfered with the induction of low-zone tolerance by monomeric BSA. The rate of non-immune elimination of BSA was found to be normal during acute malaria, and only slightly reduced in chronic infection. These results may be explained in terms of abnormal antigen handling in infected mice, due to some functional defect in macrophages, although this does not seem to be a sufficient explanation for all the phenomena of malaria-associated immunosuppression.

Animals↗
PubMed1977

Immunosuppression in murine malaria. II. The primary response to bovine serum albumin.

The primary antibody response to alumadsorbed bovine serum albumin was depressed in CBA mice infected with Plasmodium yoelii yoelii. Responses initiated within approximately 3 weeks of this malaria infection were reduced in quantity, but not in avidity. Responses initated later were normal. A depressed primary response was also seen in infected compared to control splenectomized mice; this was accompanied by impaired priming for a secondary response.

Acute Disease↗
PubMed1977

Immunosuppression in murine malaria. I. Response to type III pneumococcal polysaccharide.

Acute Plasmodium yoelii yoelii and chronic Plasmodium berghei malaria infections of CBA mice were accompanied by a reduced capacity to give an antibody response to type III pneumococcal polysaccharide (SIII). The depression of response initiated by acute malaria persisted for several weeks after recovery from clinical infection. During chronic infection, and at the peak of acute parasitaemia, virtually no response to SIII was detected. A substance which crossreacted serologically with SIII was found in blood cells of infected mice. The results suggest that antigen-specific, as well as non-specific, factors may contribute to the depression of the response to this antigen.

Animals↗