Mycobacterium bovis BCG scar status and HLA class II alleles influence purified protein derivative-specific T-cell receptor Vß expression in pulmonary tuberculosis patients from Southern India

Abstract

Purified protein derivative (PPD) RT23-recalled T-cell receptor (TCR) Vß expression was studied in the peripheral blood of 42 pulmonary tuberculosis patients and 44 healthy controls from southern India, a region where tuberculosis is endemic. Forty-eight-hour whole-blood cultures in the presence or absence of PPD-RT23 were set up, and at the end of the culture period total RNA was extracted and cDNA was synthesized. Expression of various TCR Vß families was assessed by using family-specific primers. PPD-specific expression (usage) of TCR Vß families 4, 6, 8 to 12, and 14 was found in more controls than patients. Among the responders (individuals who showed PPD-specific expression), endemic controls had significantly higher responses than the patients had for TCR Vß families 2, 3, 7, 13, and 17. The majority of the patients did not show usage of most of the TCR Vß families, and this was attributed to T-cell downregulation. A four-way nested classification analysis revealed that TCR Vß family 1, 5, 9, 12, and 13 usage in the context of HLA class II high-risk alleles (DRB1*1501, DRB1*08, and DQB1*0601) and Mycobacterium bovis BCG scar status were the determining factors in susceptibility and resistance to tuberculosis. The healthier status of controls was attributed to the wider usage of many TCR Vß families readily recalled by PPD, while the disease status of the patients was attributed to TCR Vß downregulation and the resultant T-cell (memory cell?) unresponsiveness. Host genetics (HLA status) and BCG vaccination (scar status) seem to play important roles in skewing the immune response in adult susceptibility to pulmonary tuberculosis through TCR Vß usage.