Distinct clonal repertoire of brain CD8+cells in simian immunodeficiency virus infection

Objective: Infection with simian immunodeficiency virus (SIV), like HIV, can lead to central nervous system (CNS) abnormalities. One of the alterations observed in the brain is the accumulation of highly activated CD8 lymphocytes that, while fighting the infection, may cause tissue damage. In order to determine whether these CD8 cells in the brain comprise a distinct clonal population the expression of T-cell receptor (TCR) genes of two SIV-infected monkeys with CNS abnormalities were analyzed, comparing brain to periphery. Methods: RNA from magnetically sorted CD8+ cells obtained from the brain, blood, lymph nodes, and spleen was analyzed for the distribution of 24 Vbeta family genes by reverse transcriptase-polymerase chain reaction followed by Southern blot. The CDR3 region of the most enriched family in each brain was sequenced in all the sites for comparison. Results: The pattern of Vbeta distribution in the brain and the periphery was polyclonal, but an increase in certain Vbeta families was found in the brain, suggesting that regional mechanisms participate in the determination of the local clonal specificities. The sequence of the CDR3 domain of predominant Vbeta families in the brain revealed that approximately one-third of the CD8 cells were not identified in the periphery. Conclusion: CD8 cells in the brain exhibit a distinct clonal repertoire. This distinction may have implications for regional immunity, regulation, or selection of site-specific viral mutants. (C) 2003 Lippincott Williams Wilkins.