A role for CD44 in T cell development and function during direct competition between CD44⁺ and CD44^– cells

Abstract

The role of CD44 in T cell biology remains incompletely understood. Although studies using anti‐CD44 antibodies have implicated this cell adhesion molecule in a variety of important T cell processes, few T cell defects have been reported in CD44‐deficient mice. We have assessed the requirement for CD44 in T cell development and mature T cell function by analyzing mice in which CD44–/– and WT cells were produced simultaneously. In mixed (CD44–/– + CD44+/+) bone marrow chimeras, production of CD44–/– T cells was shown to be reduced compared to WT cells due to inefficient intrathymic development. In addition, mature CD44–/– CD8+ T cells generated a substantially lower response than WT T cells after infection of mice with lymphocytic choriomeningitis virus, with the reduction in response apparent in both lymphoid and non‐lymphoid tissues. Overall, these results demonstrate a poor capacity of CD44–/– T lineage cells to compete with WT cells at multiple levels, implicating CD44 in normal T cell function.

Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation

“…Ligation of CD44 with hyaluronanis results in a variety of downstream responses that includes cell adhesion, cell migration, and hematopoietic process. In mature lymphocytes, CD44 is upregulated in response to antigenic stimuli and represents the effector stage of immunological responses505152. The use of CD44 as marker for effector T cells is generally accepted and demonstrated in various fields of studies165354.…”

Downregulation of the transcription factor KLF4 is required for the lineage commitment of T cells

“…To exclude the possibility that enforced expression of Klf4 "disguises" DN3 cells as DN2 cells by upregulating CD44 expression, the Klf4 transgene was introduced into mice on a CD44 −/− background [19]. We found that the generation of T-lineage-committed cells (DN3) remained impaired in Klf4Tg CD44 −/− mice (Supplementary information, Figure S1A and S1B).…”

An Activation Marker Finds a Function

“…Baaten et al suggest that this may be due to differences in Fas expression and reliance on Fas-mediated apoptosis, given that in their studies, Th2 cells expressed less Fas after in vitro polarization. However, Fas-mediated AICD is not confined to Th1 cells only (Krammer et al, 2007), and at least one study found that CTL responses to acute infection are markedly reduced in the absence of T cell surface expression of CD44 (Graham et al, 2007). It may be necessary to study CD44-deficient responses in the context of in vivo infection that polarizes different T cell subsets, rather than with in vitro-polarized T cells.…”