Resistance to monoclonal antibody-induced CD8+ T-cell depletion in thymectomized MHC class II-deficient mice

CD8+ T cells are present at higher than normal levels in MHC class II-deficient (IIKO) mice.

In this study, we have examined the sensitivity of CD8+ T cells to depletion induced by a single injection or multiple injections of an anti-CD8 monoclonal antibody (mAb) (2.43) in IIKO mice in vivo.

Thymectomized (ATX) IIKO mice showed the presence of a greater percentage of memory CD8+ T cells (CD44high, CD45RBlow, and MEL-14(-)) in peripheral blood lymphocytes (PBL) by 1 month after ATX compared with age-matched euthymic mice. Although CD8+ cells were not detectable in the periphery at 5 and 14 days after 2.43 injection, CD8+ T cell receptor alpha/beta+ cells expressing the memory phenotype had recovered markedly by 21 days after mAb injection in these ATX IIKO mice. The expression of CD8 beta-chain and Thy-1 as well as the absence of CD4 and of T cell receptor gamma/delta among most recovering CD8+ cells, and their varied Vbeta usage, suggested that these cells were derived from the thymus rather than from extra-thymic T-cell differentiation or from oligoclonal peripheral expansion. In addition, low numbers of CD8+ cells that were coated with mAb (2.43) were detected in the lymph nodes of ATX IIKO mice 7 days after mAb injection. Most of these nondepleted lymph node CD8+ cells expressed the memory phenotype and low levels of CD8beta. Furthermore, the levels of recovering CD8+ cells in PBL of ATX IIKO mice by 21 days after mAb treatment were markedly higher than those in PBL of simultaneously mAb-treated ATX wild-type (B10) mice.

Together, these studies indicate that memory CD8+ T cells are relatively resistant to mAb-induced depletion in vivo.