Cooperation in organisms, whether bacteria or primates, has been a difficulty for evolutionary theory since Darwin. On the assumption that interactions between pairs of individuals occur on a probabilistic basis, a model is developed based on the concept of an evolutionarily stable strategy in the context of the Prisoner's Dilemma game. Deductions from the model, and the results of a computer tournament show how cooperation based on reciprocity can get started in an asocial world, can thrive while interacting with a wide range of other strategies, and can resist invasion once fully established. Potential applications include specific aspects of territoriality, mating, and disease.

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The Evolution of Cooperation

Four previously healthy homosexual men contracted Pneumocystis carinii pneumonia, extensive mucosal candidiasis, and multiple viral infections. In three of the patients these infections followed prolonged fevers of unknown origin. In all four cytomegalovirus was recovered from secretions. Kaposi's sarcoma developed in one patient eight months after he presented with esophageal candidiasis. All patients were anergic and lymphopenic; they had no lymphocyte proliferative responses to soluble antigens, and their responses to phytohemagglutinin were markedly reduced. Monoclonal-antibody analysis of peripheral-blood T-cell subpopulations revealed virtual elimination of the Leu-3 / helper/inducer subset, an increased percentage of the Leu-2 + suppressor/cytoxic subset, and an increased percentage of cells bearing the thymocyte-associated antigen T10. The inversion of the T/ helper to suppressor/cytotoxic ratio suggested that cytomegalovirus infection was an important factor in the pathogenesis of the immunodeficient state. A high level of exposure of male homosexuals to cytomegalovirus-infected secretions may account for the occurrence of this immune deficiency.

Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency.

Epstein-Barr virus.

Head and neck cancer.

A human leukemic cell line (THP-1) cultured from the blood of a boy with acute monocytic leukemia is described. This cell line had Fc and C3b receptors, but no surface or cytoplasmic immunoglobulins. HLA haplotypes of THP-1 were HLA-A2, -A9, -B5, -DRW1 and -DRW2. The monocytic nature of the cell line was characterized by: (1) the presence of alpha-naphthyl butyrate esterase activities which could be inhibited by NaF; (2) lysozyme production; (3) the phagocytosis of latex particles and sensitized sheep erythrocytes; and (4) the ability to restore T-lymphocyte response to Con A. The cells did not possess Epstein-Barr virus-associated nuclear antigen. These results indicate that THP-1 is a leukemia cell line with distinct monocytic markers. During culture, THP-1 maintained these monocytic characteristics for over 14 months.

Establishment and characterization of a human acute monocytic leukemia cell line (THP‐1)

Henle, Gertrude (Children's Hospital of Philadelphia, Philadelphia, Pa.), and Werner Henle. Immunofluorescence in cells derived from Burkitt's lymphoma. J. Bacteriol. 91:1248-1256. 1966.-Indirect immunofluorescence tests led to the brilliant staining of a small proportion of the cells in five different cultures derived from Burkitt's (African) lymphomas. The reaction was not restricted to the 17 sera from cases of this disease but extended to many sera from American individuals, whether healthy donors or patients suffering from a variety of illnesses. The incidence of positive sera increased with age from about 30% in childhood to > 90% in adults. Fluorescein-isothiocyanate-conjugated human gamma-globulins were suitable for direct staining of the same proportion of cells. The stained cells appeared to be in varying stages of degeneration, but cultural conditions leading to an increase in the cellular death rates failed to result in a rise in fluorescent cells. Several observations suggest that the stainable cells might be those which are seen to harbor virus particles under the electron microscope. Two cell lines derived from leukemic patients in this country also contained a small fraction of stainable cells but two others, and numerous primary human leukocyte cultures, gave consistently negative results. Attempts to relate the staining to known viral antigens have failed to implicate herpes simplex, varicella, cytomegalo, and reo viruses types 1, 2, and 3. The nature of the virus carried by the lymphoma cells as well as of the staining reactions remains to be determined.

Immunofluorescence in Cells Derived from Burkitt's Lymphoma

Epstein–Barr Virus in Burkitt's Lymphoma and Nasopharyngeal Carcinoma: EBV DNA in Biopsies of Burkitt Tumours and Anaplastic Carcinomas of the Nasopharynx

EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx.

A herpes-type virus has been detected with remarkable frequency in cell lines derived from Burkitt's lymphomas, leukemic tissues, or buffy coats of a variety of patients and healthy donors.'-8 This agent is being named EB virus (EBV), for convenience, after the cell lines in which it was first observed.' M\\ost of the virus particles seen by electron microscopy in a small proportion of the cells are judged noninfectious because they are defective.\" 9. 10 To date, EBV has been transmissible only to cultured human cells of the hematopoietic system.\"'12 Virus-producing cells are readily detectable by indirect immunofluorescence tests with various human sera or by direct staining with fluorescein isothiocyanate-conjugated human y-globulins.'3'-7 Attempts to identify the agent by appropriate virus-specific immunofluorescence tests have failed. Thus EBV appears to be a new member of the herpes group.'3-\"5 From human serum surveys it is evident that infections by EBV, or a close relative of it, are frequent, and that the agent has a world-wide dissemination.\"3 117, 18 The age distribution of antibodies to EBV among American children parallels that of antibodies to other common viruses, such as measles, mumps, or poliomyelitis in the prevaccination era. 18 Except for the fact that all Burkitt's tumor patients studied thus far'3 1' and a high percentage of patients with carcinomas of the postnasal spaces'9 were found to have high titers of antibodies to EBV antigens, no other suggestive relationship of the virus to known disease entities has been recorded. The present report indicates that EBV is related to, and probably the cause of, infectious mononucleosis. Materials and Methods.-The techniques for growth and maintenance of cell lines derived from Burkitt's tumors have been described, as well as the procedures for preparation of cell smears, detection of EB virus antigens, and corresponding antibodies by immunofluorescence.3, 16 Cells of the EB-3 line were routinely used, which had been kept for 4-7 days on arginine-deficient Eagle's basal medium with 25% fetal calf serum (BME25) obtained by preincubation at 370C for 7 days or merely by omission of the amino acid. The arginine deficiency inhibits cellular growth but increases the number of EBV antigen-producing cells by a factor of 5-10 (to be published). Results.-The indirect immunofluorescence test for antibodies to EB virus was used in a search for illnesses that might be caused by this agent. In one series of tests, paired acute stage and convalescent sera from pediatric patients with unidentifiable viral infections were examined with negative results.18 As another approach, serial sera were tested that had been collected from children in prospective studies of viral infections. Such sets of sera were kindly supplied by Dr. John P. Fox from the \"New York Virus Watch,\" and by Dr. John H. Dingle from the Cleveland Family Study. Of the first group, 33 sets were examined that had been collected over periods of from one to four

https://www.pnas.org/content/pnas/59/1/94.full.pdf

Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis.

Stimulated by a report on elevated IgA levels in nasopharyngeal carcinoma (NPC), we tested a total of 372 sera from patients with NPC, other carcinomas of head and neck or elsewhere, Burkitt's lymphoma (BL), infectious mononucleosis (IM) or healthy controls. The sera were titrated in indirect immunofluorescence tests for IgA antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and to the diffuse (D) or restricted (R) components of the EBV-induced early antigen (EA) complex. The results proved NPC to be outstanding in that prior to therapy 93% of the patients tested revealed IgA antibodies to VCA and 73% to D, often at high titers which occasionally matched the corresponding IgG antibody levels. The EBV-specific IgA titers increased from stages I or II to stages III or IV; i.e. with the total tumor burden. Conversely, many of the NPC patients examined 2-6 years after initial therapy had only low levels of EBV-specific IgA or none at all, and the majority of those with high titers were known to have residual or recurrent disease. In contrast to untreated NPC patients, less than 5% of 73 patients with other carcinomas or of 76 healthy donors revealed VCA-specific IgA and even fewer EA-specific IgA; only 28% and 4% of 54 BL patients tested at admission had IgA antibodies to VCA and R, respectively, and 38% and 3% of 37 IM patients showed transient VCA- or D-specific IgA responses, all at generally low titers. While sera from untreated NPC patients often contained IgA antibodies also to herpes simplex type 1 virus, their incidence and range of low titers were similar to those obtained with sera from patients with other carcinomas or from healthy donors. It thus appears that the elevated IgA levels in NPC might be due to EBV-specific antibodies. Possible reasons for this unique response in NPC have been discussed.

Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma.

Inoculation of 64-10 or Raji cultures with Epstein-Barr virus derived from the HRI-K clone of the P3J Burkitt's lymphoma line caused abortive infections in most of the lymphoblastoid cells with synthesis of "early antigens" but few, if any, capsids. Antibodies to early antigens were detected by indirect immunofluorescence in serums of many patients with infectious mononucleosis, Burkitt's lymphoma, or nasopharyngeal carcinoma. These antibodies were rarely present in other serums even though some of them showed high titers of antibodies to Epstein-Barr virus when assayed on EB3 Burkitt tumor cells; they also prevented synthesis of early antigens, provided the serums were mixed with the virus prior to inoculation. Antibodies to early antigens possibly reflect current or recent disease processes that are associated with the virus.

https://science.sciencemag.org/content/sci/169/3941/188.full.pdf

Gertrude Henle

Papers

Immunofluorescence in Cells Derived from Burkitt's Lymphoma

EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx.

Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis.

Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma.

Differential Reactivity of Human Serums with Early Antigens Induced by Epstein-Barr Virus