Kevin S. Byron

Severe Herpesvirus Infections in an Adolescent without Natural Killer Cells

NATURAL killer cells are a population of T-cell–receptornegative (CD3–) lymphocytes that spontaneously mediate the lysis of sensitive target cells. Natural killer cells are similar morphologically ...

X-linked lymphoproliferative syndrome. Natural history of the immunodeficiency.

The X-linked lymphoproliferative syndrome is characterized by immunodeficiency to Epstein-Barr virus (EBV) manifested by severe or fatal infectious mononucleosis and acquired immunodeficiency. We studied immune responses in six males of a well-characterized kindred with the X-linked lymphoproliferative syndrome. Two males were studied before and during acute fatal EBV infection. Both individuals demonstrated normal cellular and humoral immunity before EBV infection. During acute EBV infection, both individuals developed vigorous cytotoxic cellular responses against EBV-infected and -uninfected target cells. Anomalous killer and natural killer T cell activity was demonstrated against a variety of lymphoid cell lines, autologous fibroblasts and autologous hepatocytes. Effector cells responsible for anomalous killing reacted with a pan-T cell monoclonal antibody, and belonged to the OKT.8 T cell subset. Death in each case was caused by liver failure, but one patient developed extensive liver necrosis, whereas the other developed a massive infiltration of the liver with EBV-infected immunoblasts after aggressive immunosuppressive therapy. Immunological studies were performed on four males who had survived EBV infection years previously. They demonstrated global cellular immune defects with deficiencies of lymphocyte proliferative responses to mitogens and antigens, humoral immune deficiencies, abnormalities of regulatory T cell subsets and deficient natural killer cell activity. We propose that an aberrant immune response triggered by acute EBV infection results in unregulated anomalous killer and natural killer cell activity against EBV infected and uninfected cells. These studies suggest that global immune defects appearing in males with X-linked lymphoproliferative syndrome who survive EBV infection are epiphenomenon.

Hemophiliac immunodeficiency: Influence of exposure to factor VIII concentrate, LAV/HTLV-III, and herpesviruses

The relationship between hemophiliac immunodeficiency and exposures to factor VIII concentrate, LAV/HTLV-III retrovirus, and infection with Epstein-Barr virus and cytomegalovirus was examined. Exposure to factor VIII concentrate was significantly correlated with decreased percentages of T helper/inducer cells, decreased T helper/suppressor cell ratios, and decreased proliferative responses to plant mitogens. LAV/HTLV-III seropositivity was the primary predictor of increased percentages of HLA-DR-bearing mononuclear cells and decreased proliferative responses to pokeweed mitogen. Epstein-Barr virus and cytomegalovirus infections acted in a synergistic manner with LAV/HTLV-III to produce immunoregulatory defects. Increased percentages of T suppressor cells and decreased delayed cutaneous hypersensitivity skin test responses were observed in LAV/HTLV-III seropositive hemophiliacs infected with Epstein-Barr or cytomegalovirus. We conclude that hemophiliacs receiving commercial factor VIII concentrate experience several stepwise incremental insults to the immune system: alloantigens in factor VIII concentrate, LAV/HTLV-III infections, and herpesvirus infections.

Treatment of life-threatening Epstein-Barr virus infections with acyclovir☆

Two pediatric patients with life-threatening Epstein-Barr virus infections were studied immunologically and treated with acyclovir [9-(2-hydroxyethoxymethyl) guanine]. The patient with chronic active Epstein-Barr virus infection who experienced massive hepatosplenomegaly, pancytopenia, and failure to thrive demonstrated abnormalities of T and B lymphocytes. A second patient, with the X-linked lymphoproliferative syndrome, experienced a rapidly fatal course of acute Epstein-Barr virus infection which typifies this yet undefined immunodeficiency to Epstein-Barr virus. In each case, objective evidence for clinical improvement or antiviral effect of acyclovir treatment was not apparent. Abnormally productive Epstein-Barr virus infections did not appear to play a major role in the clinical syndromes observed. Current studies are focused on treatment of immunologically normal patients with early complicated Epstein-Barr virus infection.

Detection of HIV in Clinical Specimens

A 24 kilodalton protein (p24), immunologically distinct from proteins in most other retroviruses, has been demonstrated to be a major structural core component of HIV-1 [1-5]. Several studies have shown that there are changing patterns of HIV-1 p24 antigen and antibody during the progression of clinical disease [6,7]. Antigen is virtually undetectable and antibody is in excess during the early, asymptomatic stage [2-4,8-12]. The onset and progression of disease is preceded by a marked decrease in antibody, which is then followed by an increase in antigen [ibid.]. Although non-virus-associated protein can be present in both plasma and tissue culture supernatant, the measurement of p24 protein is an acceptable approximation to measure the amount of virus in fluids. The preparation of a mouse monoclonal antibody with high specificity and affinity for the viral p24 protein has allowed the development of an extremely sensitive ELISA for HIV-1 p24 core antigen as well as a highly specific test for the measurement of HIV-1 anti-p24 binding capacity. Different companies have developed p24 core antigen detection kits. We present here protocols adapted from the Du Pont p24 Core Profile ELISA.