Compartmentalization of TCR repertoire alteration during rejection of an intrabrain xenograft.

ABSTRACT

Xenograft rejections of embryonic pig neural cells implanted into the adult rat striatum occurs within 3-4 weeks, following a dramatic T cell infiltration. Little is known about the cross-talk between the brain and peripheral lymphoid tissues which results in this recruitment and lymphocyte homing. To better characterize the dynamics of the T cell response against xenogeneic neural cells implanted into the brain parenchyma, we used both qualitative and quantitative methods to follow the alterations of the CDR3 length distribution (CDR3-LD) of the TCR (T cell receptor) beta chain in the transplanted striatum and compared this response to that observed in the deep cervical lymph nodes, spleen, and blood. Data showed that the T cell repertoire diversity was highly altered in the recipient brain during xenograft rejection. Comparison of the alterations of the CDR3-LD between several animals revealed a single public alteration in the Vbeta20 family, and many private alterations of the CDR3-LD which differed from one infiltrated brain to another. Alterations of the T cell repertoire were also observed in lymphocytes homed into the deep cervical lymph nodes. However, they differed from the alterations detected in the infiltrated brains. Conversely, no significant alteration of the CDR3-LD was detected in the spleen or in the blood. These data suggest that the deep cervical lymph nodes play an active role in the process of xenograft recognition or/and rejection. However, they also indicate that the fate of T cells homed in the brain and deep cervical lymph nodes differs.