Strong alpha beta and gamma delta TCR response in a patient with disseminated Mycobacterium avium infection and lack of NK cells and monocytopenia.
Infection with atypical mycobacteria occurs mainly in patients with a compromised cellular immune system, in particular in those with a defective T cell or monocyte function. Here we analyzed the specific immune response of an adolescent HIV-negative patient with disseminated mycobacterium avium infection and fatal varizella zoster virus infection. The patient presented with dysplastic hematopoesis of all cell lineage's and a bicytopenia of erythrocytes and leukocytes, but a hematological malignancy could not be found. We found a peripheral lymphopenia and monocytopenia, as well as a lack of NK-cells and B-cells. Lymphocytes consisted of 95% T cells, which contained up to 40% of TCR gammadelta+CD4-CD8-T-cells (mainly TCR gamma9delta2), few monocytes and B-cells. Approximately 50% of CD3+ T-cells showed a CD57+ NK-like phenotype. Functional analysis of PBMC revealed a good antigen-specific T cell function if antigen-presenting cells were supplemented from a HLA-matched donor. Moreover, a strong M. avium specific cytotoxicity mediated by TCR alphabeta+T-cells could be found in vitro and even ex vivo. In contrast, NK-killing was absent. No evidence for a defect in IL-12 or IFN-gamma production and signaling were found. The data indicate that a strong alphabeta and gammadelta T cell immunity tries to compensate for a deficient monocyte and NK cell function in this patient.
Wendland
T
T
Clinic for Rheumatology and Clinical Immunology/Allergology, University Hospital Bern, Freiburgstrasse, CH-3010, Bern, Switzerland.
Herren
S
S
Yawalkar
N
N
Cerny
A
A
Pichler
W J
WJ
D000293:Adolescent; D000328:Adult; D002644:Chickenpox / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology*; D007970:Leukopenia / Q000276:immunology* / Q000821:virology; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000276:immunology* / Q000821:virology; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000097:blood / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta