Predominance of Vγ9/Vδ2 T Lymphocytes in the Cerebrospinal Fluid of Children with Tuberculous Meningitis: Reversal after Chemotherapy

Abstract

Background: We analyzed the-y6 T cell composition and responses in the peripheral blood and cerebrospinal fluid (CSF) of children affected by tuberculous meningitis (TBM) and in control children. Materials and Methods: Peripheral blood and CSF samples were stimulated with different phosphoantigens and IL-2, and expansion of Vy9/V62 T cells assessed by FACS analysis. Vy9/V82 lines were obtained by culturing CSF or peripheral blood mononuclear cells (PBMC) in vitro with phosphoantigens and 1L-2 for 2 months, and tested for proliferation and cytokine production in response to phosphoantigens. V52(D)J5 junctional sequence length was assessed by PCR. Results: The repertoire of y6 T cells from the CSF of TBM patients was characterized by the predominance of Vy9/VS2 T lymphocytes, which accounted for >80% of ,y6 T cells. Vy9/V82 cells from the CSF of TBM children responded to different synthetic and natural (mycobacterial) phosphoantigens and produced discrete amounts of IFN-y and TNF-a. The in vitro expansion of V-y9/V82 T cells from CSF and peripheral blood of TBM patients prominently decreased following chemotherapy, and sinilarly, the proportion of ex vivo unstimulated V-y9/ V82 T cells in CSF of TBM patients decreased to levels detected in the CSF of control subjects. V82 CDR3 TCR analysis showed that the remaining V82 cells in the CSF of TBM patients were still polyclonal. Conclusions: These findings are consistent with an involvement of Vy9/V82 T cells in TBM.

Features in Tubercular Meningoencephalitis Diagnosis: 18 Childhood Cases

“…These radiological technologies aid early diagnosis, suggesting a tuberculosis etiology based on major involvement of the basal encephalic region: hyperdensity in the basal cisterns seems to be typical of CNS-TB, although it is not a very sensitive finding (Naeisseria infection and subarachnoid hemorrhage are also reported as causes of hyperdensity in the basal cistern). All the neuroradiological investigations conducted on our patients revealed the thickening and intense enhancement of the meninges and, in accordance with the literature [7] , a frequent basal cistern involvement.…”

“…Diagnostic evaluation includes tuberculin skin tests, chest radiography and other imaging studies, smear culture, examination of cerebrospinal fluid and polymerase chain reaction, as well as more recent immunological assays such as interferon-γ or γδ T cells [6,7] . Modern imaging is a cornerstone of early CNS-TB diagnosis and may help to prevent unnecessary morbidity and mortality.…”

γδ T-APCs: a novel tool for immunotherapy?

“…infections compared to HMB-PP -infections, suggesting increased recruitment and/or proliferation in response to HMB-PP released by invading bacteria [30,31]. High cd T cell levels do not persist and decline to normal levels during antimicrobial treatment [32]. This hyper-responsiveness of adult Vc9/Vd2 T cells to HMB-PP may be the result of a memory compartment established in newborn babies during exposure to environmental and/or pathogenic microbes [1,33].…”

Vγ9 / Vδ2 T lymphocytes reduce the viability of intracellularMycobacterium tuberculosis

“…Polyclonal V + 9/Vˇ2 T cell lines were prepared as previously described [46,47]. Briefly, PBMC were obtained from healthy PPD + volunteers by Ficoll-Hypaque (Pharmacia, Uppsala, Sweden) gradient centrifugation.…”