Activation of gamma delta T cells in the primary immune response to Mycobacterium tuberculosis.

Although the immunologic role of T cells bearing the conventional alpha beta T cell receptor (TCR) has been well characterized, little is known about the function of the population of T cells bearing the gamma delta TCR. Therefore, the role of gamma delta T cells in the immune response to Mycobacterium tuberculosis (MT) was investigated. The number of TCR gamma delta cells in the draining lymph nodes of mice immunized with MT was greatly increased in comparison with the number of TCR alpha beta cells. Three biochemically distinct gamma delta TCRs were detected. Analyses of cell cycle, of interleukin-2 receptor expression, and of interleukin-2 responsiveness showed that a large proportion of the gamma delta T cells were activated in vivo. TCR gamma delta cells responded to solubilized MT antigens in vitro but, in contrast to MT-specific alpha beta T cells, the response of gamma delta T cells to MT did not require major histocompatability complex class II recognition. These results provide an example of antigen-specific activation of gamma delta T cells in vivo and indicate that gamma delta T cells may have a distinct role in generating a primary immune response to certain microorganisms.

Lumbar puncture for evaluation of latent syphilis in hospitalized patients. High prevalence of cerebrospinal fluid abnormalities unrelated to syphilis.

OBJECTIVE: To determine the prevalence of abnormal neurologic findings and cerebrospinal fluid abnormalities in hospitalized patients with serologic evidence of latent syphilis. DESIGN: Cross-sectional survey. METHODS: Consecutively admitted hospital inpatients from an inner-city population were screened for serologic evidence of syphilis with reactive plasma reagin and confirmatory fluorescent treponemal antibody absorption assays. In those with reactive tests, such clinical findings as a history of treatment for syphilis, neurologic abnormalities, presence of human immunodeficiency virus infection, and rapid plasma reagin titer were correlated with cerebrospinal fluid white blood cell count, protein level, and VDRL result. RESULTS: Of 490 consecutive patients, 52 (11%) had serologic evidence of syphilis. Forty-three (83%) of these underwent lumbar puncture. Of the 43, 31 (72%) were seronegative for human immunodeficiency virus and 12 (28%) were seropositive. No patient had a reactive cerebrospinal fluid VDRL test. Cerebrospinal fluid abnormalities were seen in 32% of human immunodeficiency virus-seronegative patients and in 67% of human immunodeficiency virus-seropositive patients. Cerebrospinal fluid abnormalities were not predicted by history of treatment for syphilis, abnormal neurologic findings, or an elevated rapid plasma reagin titer. Cerebrospinal fluid IgG indexes in patients with elevated cerebrospinal fluid protein levels suggested that the protein abnormalities were not caused by local antibody production. Nonreactive cerebrospinal fluid fluorescent treponemal antibody absorption tests suggest that the cerebrospinal fluid abnormalities were not the result of neurosyphilis. CONCLUSIONS: There was a high prevalence of cerebrospinal fluid abnormalities in hospitalized patients with latent syphilis detected by routine screening. Because of the nonspecificity of the cerebrospinal fluid findings, routine lumbar puncture for such patients appears to contribute little to the treatment of latent syphilis.

Tuberculin skin test reactivity, anergy, and HIV infection in hospitalized patients. Longcope Firm of the Osler Medical Housestaff.

PURPOSE: Detection of latent tuberculosis infection is an important step in the control of tuberculosis because high-risk persons may be given preventive therapy. The value of tuberculin skin testing in individuals with human immunodeficiency virus (HIV) infection, however, is limited by anergy. We evaluated the prevalence of tuberculin skin test reactivity, anergy, and HIV infection in a group of hospitalized patients in an area where both tuberculosis and HIV infection are prevalent. PATIENTS AND METHODS: Three hundred fifty-one patients consecutively admitted to a medical service of a large urban teaching hospital were enrolled in the study. All those with no documented history of a positive tuberculin skin test were evaluated on admission with purified protein derivative (PPD) by the Mantoux test, and with anergy testing using a multiple-puncture device. HIV testing was offered to all patients who did not have a known history of HIV infection, and was performed when informed consent was obtained. RESULTS: Forty-one patients (12%) had a documented history of a positive PPD. Of the remaining 310 patients, 62 (20%) had a PPD response of > or = 10 mm induration. Fifty-two (15%) of the 351 patients were HIV positive. None of the HIV-infected patients was PPD positive. Anergy was found in 63% of the HIV-infected patients and 28% of the HIV-seronegative patients. Independent risk factors for a positive PPD included age > 55, male sex, and hypertension. HIV infection, current steroid use, and a history of cancer were associated with a negative PPD. Independent risk factors for anergy included HIV infection, current corticosteroid use, renal failure pneumonia, and a history of cancer. Of the 62 new PPD-positive patients, 30 (48%) were candidates for chemoprophylaxis. Additionally, 30 (63%) of 48 HIV-seropositive patients who were completed testing were anergic and might be candidates for chemoprophylaxis. Almost all of the patients eligible for chemoprophylactic therapy would have been detected if only patients at increased risk for developing tuberculosis were screened. CONCLUSIONS: Tuberculosis infection, HIV infection, and anergy were common in patients admitted to this medical service. Interpretation of PPD reactivity was confounded by a high prevalence of anergy, particularly in HIV-infected patients. A large proportion of patients tested were candidates for chemoprophylaxis. Routine tuberculin skin testing with anergy testing for high-risk patients on admission to the hospital is useful for identifying patients who might benefit from prophylaxis to help control the spread of tuberculosis.

Mapping of the gene for the tyrosine kinase Itk to a region of conserved synteny between mouse chromosome 11 and human chromosome 5q.

The protein-tyrosine kinase gene Itk is expressed preferentially in T lymphoid cells of the mouse and is induced by IL-2. A related gene, Btk, is expressed in the murine B lymphoid and myeloid lineages. Because mutations in Btk and the corresponding human gene are associated with X-linked immunodeficiency syndromes, it was of interest to map Itk and its human counterpart. By Southern blot analysis of DNA from the progeny of two multilocus crosses, murine Itk was mapped to Chromosome 11. By fluorescence in situ hybridization, human ITK was mapped to 5q32-q33. Murine Itk and its human homologue lie within regions of conserved synteny that include several growth factor and growth factor receptor genes. This region in humans is frequently deleted in the myelodysplastic syndrome, suggesting possible involvement of ITK in this disorder.