Follicles in gut-associated lymphoid tissues create preferential survival niches for follicular Th cells escaping Thy-1-specific depletion in mice

Although a substantial number of T cells may escape depletion following in vivo mAb treatment in patients undergoing immunosuppression, their specific tissue location and phenotypic characteristics in different peripheral lymphoid tissues have not been analyzed in detail. Here we investigated the survival of CD4(+) T cells immediately following anti-Thy-1 mAb treatment in mice. We found a preferential survival of CD4(+) T cells expressing Thy-1 antigen in the Peyer's patches (PP) and also in mesenteric lymph nodes (MLN), where the relative majority of the surviving CD4(+) T cells displayed CD44(high)/CD62L(-) phenotype corresponding to effector memory T-cell features. These CD4(+) T cells also expressed CXCR5 and PD-1 (programmed cell death-1) markers characteristic for follicular T-h cells (T-FH). We also demonstrate that the immediate survival of these cells does not involve proliferation and is independent of IL-7. Induction of germinal center formation in spleen enhanced while the dissolution of follicular architecture by lymphotoxin-beta receptor antagonist treatment slightly reduced T-FH survival. Our results thus raise the possibility that the follicles within PP and MLN may create natural support niches for the preferential survival of T-FH cells of the memory phenotype, thus allowing their escape during T-cell depletion.