Helen Lipscomb

Delayed Onset of Infectious Mononucleosis Associated with Acquired Agammaglobulinemia and Red Cell Aplasia

In 1974, an 11-year-old white boy with the X-linked lymphoproliferative syndrome developed hyper-IgM after becoming infected with Epstein-Barr virus. However, he failed to develop normal immune responses against the virus. In December 1981, when red cell aplasia occurred, he was given packed erythrocytes and gammaglobulin. Nine weeks later, acute infectious mononucleosis developed. Concurrently, his T4/T8 helper/suppressor ratio decreased from 2.7 to 0.2, and IgM antibodies to Epstein-Barr virus appeared. Subsequently, circulating B cells became undetectable in his blood, and agammaglobulinemia appeared. Red cell aplasia abated transiently. This patients course was complicated by Haemophilus influenzae and Mycobacterium tuberculosis pneumonias, and red cell aplasia and agammaglobulinemia have persisted. Epstein-Barr virus acting as a slow virus probably induced the red cell aplasia and agammaglobulinemia because of the aberrant immune responses to Epstein-Barr virus. Immunodeficient responses to Epstein-Barr virus should be sought in other patients with the diseases documented in our patient.

The effect of neonatal thymectomy on the induction of autoimmune orchitis in rats.

The objective of these experiments was to determine the effects of neonatal thymectomy on the induction of experimental autoimmune orchitis in inbred rats of the Fischer 344 and Lewis strains. It was found that thymectomy alone in Lewis rats, and thymectomy followed by immunization with testicular extract in both Lewis and Fischer 344 rats, led to the development of autoimmune orchitis, as indicated by decreased testes weights, increased serum spermagglutinating antibody titers and histopathological changes in the testes. These data indicate that rats of the Lewis strain are genetically predisposed to the development of autoimmune orchitis, and thymectomy alone leads to active manifestations of the disease, which are further enhanced by subsequent immunization with testicular extract. In Fischer 344 rats, thymectomy followed by immunization leads to indications of early signs of experimental autoimmune orchitis. This is in contrast to experimentally induced autoimmune diseases in other model systems, where previous investigators have reported that thymectomy lessens or prevents induction of autoimmune disease. It is suggested that these differences may be related to the timing of thymectomy with regard to differences in the time of appearance of sperm antigens (at puberty) as compared to pre-natal and early neonatal appearances of other autoantigens.

Effects of reduced food intake on morphometry and cell production in the small intestine of the rat

SummaryThe present study examined the effects of a 60% reduction in food intake on kinetic and morphometric parameters in the small intestine of adult male Lewis rats. We observed that, after 20 days, the wet weight of jejunum and ileum, thickness of muscularis externa of duodenum, crypt depth throughout the intestine, and DPM/mg and DPM/crypt in ileum were decreased in animals on reduced food intake when compared to their paired, normally fed controls. These results demonstrated that reduced food intake caused distinctive effects focused primarily in the ileum, thus opening to question the use of the technique of pair feeding as a control for studies of intestinal cell proliferation in which manipulations of the animals result in altered food intake or body weight.

A method for determination of antibody-dependent cellular cytotoxicity (ADCC) of human peripheral mononuclear cells☆

A method is described for measuring antibody-dependent cellular cytotoxicity (ADCC) of mononuclear cells from human peripheral blood using an established murine cell line and commercially prepared antisera. The test utilizes a standard 51Cr release technique. The ADCC activity of mononuclear cells obtained from 10 healthy human volunteers was measured at 4 different effector: target cell ratios. A linear relationship between %51Cr release (ADCC) and the number of effector cells was observed.

Chromosome aberrations in peripheral lymphocytes of male homosexuals

Karyotypes of peripheral lymphocytes of 19 male homosexuals showed increased hypodiploidy. Chromosomes #19 and #20 were most frequently lost. Also, structural chromosome aberrations frequently occurred consisting chiefly of translocations and simple chromosome breaks. Terminal deletions, inversions, and isochromosomes occurred less commonly. In three of the cases, 100% of the cells were involved in a pericentric inversion of a chromosome #9. Chromosomes #3 in p21.1 and 1 in p32.3 were repeatedly affected. Structural aberrations were seen less frequently in men with acquired immunodeficiency syndrome(AIDS) and AIDS-related complex than in asymptomatic homosexuals. The hypodiploidy with preferential loss of chromosomes was constantly present. The marker chromosomes and simple breaks at repeated sites are another manifestation of damage to the immune system in these male homosexuals from Greenwich Village in New York City. The chromosomal damage was potentially the result of exposure to amyl and butyl nitrites, viral infections, or immunologic reactions to sperm, which crossreact with lymphocytes.

In-vitro infection of chronic lymphocytic leukemia cells by Epstein-Barr Virus (EBV)

We sought to determine the potential of infecting lymphoid cells from patients with chronic leukemia (CLL) with Epstein-Barr virus (EBV) by testing for EBV receptors (EBVR) by flow cytometry, assessing for infectability of these cells by culturing with B95-8-derived virus, and staining for EB nuclear-associated antigens (EBNA) at various times post-infection. EBVR were present on 54-91% of lymphoid cells in seven cases of CLL and on 46% of prolymphocytic leukemia cells. Dynamic changes regarding EBNA positivity, morphology, and viability occurred post-infection with the virus. On day 2 only a few EBNA-positive lymphoblasts were observed. On days 11-21 positivity increased from 2 to 34% of cells. Simultaneously, the viable cell number declined to approximately 1/10th of original number. A significant proportion of the EBNA-positive cells corresponded to the original CLL cells. In 3 of 7 cases of CLL a Pan T-cell phenotype was demonstrated by Leu-1 monoclonal antibody testing. The infected cells did not react with two monoclonal antibodies, EBV-CS 1 and 4, which react with B-cell lymphoblastoid cell lines (B-LCL). Moreover, the B-LCL derived at 1-2 months post-infection of CLL cells did not express the Leu-1 antigen, but expressed EBV-CS 1 or 4 defined antigens. In the prolymphocytic leukemia, 64% of the cells showed EBNA positivity on day 7 and giant cells with huge round or multiple nuclei appeared which were EBNA-positive. CLL and prolymphocytic leukemia cells can be infected as demonstrated by EBNA-positivity. This infection does not lead to immediate transformation, but evokes lymphoblast and multinucleated giant cell production prior to the death of cells.

Responses to Epstein-Barr Virus in Immune Deficient Patients

Two decades have passed since Epstein-Barr virus (EBV) was described (1) and yet new diseases continue to be attributed to the virus. Debates initiated in the early 1960’s are ongoing regarding the role of the virus in Burkitt lymphoma (BL), and nasopharyngeal carcinoma (NPC). Recently, the opportunistic malignant lymphomas (ML) occurring in immune deficient individuals have provided new puzzles. Questions remaining to be answered are whether latent virus is activated in B cells transformed by other agents or alternatively, does the virus infect the malignant B cell after transformation owing to the presence of viral receptors on the cell. Attention has also been directed to find oncogenic and benign strains of the virus. In our view, underlying inherited or environmentally induced immune deficiency is important in determining the outcome of EBV infections.

Thymectomy modifies androgenizing effects of a testis transplant during critical period for neuroprogramming

Thymectomy simultaneous with transplantation of a syngeneic testis from a littermate to Fischer 344 rats ameliorated the androgenizing effects of the testis transplant on ovarian morphology at 90 days of age.

Alterations in bone-marrow cellularity following thymectomy in rats.

The number of nucleated marrow cells was decreased following neonatal thymectomy in rats, and was corrected by administration of syngeneic lymphoid cells, or by implantation of a syngeneic testis. These results suggest that, in the rat, as has been shown previously in the mouse, lymphoid cells exert parital control over bone marrow cellularity and this effect may be further modulated by sex steroids.