Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 106

3.9 Lymphocytes

Lymphocytes (L m) have a very large nucleus. Lymphocyte is much

smaller than the 3 types of granulocytes. They account for 25-35% of leukocytes.
They regulate adaptive immunity. The major production sites of T and B cells are the
thymus and bone marrow, respectively. Both B and T lymphocytes reside in lymph
nodes and in the spleen, where they mature into fully functional cells.
Cell history can lead to tissue-specific cells according to the residential type
of lymphoid organs, but this property can be reverted. Effector cell behavior is
influenced by cytokines involved in helper T H1 and T H2 responses. T-cell exit from
lymphoid and peripheral tissues requires sphingosine 1-phosphate and chemokine
CC-motif receptor CCR7, respectively.
B lymphocytes as well as some types of T lymphocytes, such as CD4

ϕ ; size 8-15

+ ,CD8 + ,

α , and NK (natural killer) T cells, constitute distinct lineages that do not

interconvert. On the other hand, other T-cell lineages can remodel in other T-cell
types, such as helper and inducible T Reg lymphocytes.
Both CD4 and CD8 that bind to major histocompatibility complex molecules
lodge on immature, double-positive thymocytes. Double-positive thymocytes with
a T-cell receptor that interacts weakly with self-peptides bound to MHC molecules
undergo a positive selection to become single-positive CD4

/ β , γ / δ

T lympho-
cytes. Double-positive thymocytes with a TCR that links strongly to self-peptide
bound to MHC molecules undergo a negative selection and apoptosis, thereby
preventing the development of self-reactive T lymphocytes. Positive selection relies
on a moderate, sustained Ca 2 + import and ERK activation [ 202 ]. On the other hand,
high-affinity TCR ligands — negative selectors — cause high magnitude, short
duration Ca 2 + import and ERK activation. Increase in cytosolic Ca 2 + concentration
induced by TCRs that activates T cells results from the stimulation of the PLC

+ or CD8 +

1-
IP 3 axis. 93 In response to weak TCR ligands, Na V 1.5 bound to the regulatory Na V β

γ

4

subunit favors a sustained calcium entry [ 202 ]. 94

3.9.1 Selection between CD4 and CD8 Coreceptors

Coreceptors CD4 and CD8 intervene in the recognition of major histocompatibility
complex class-2 and -1 ligands, respectively, as well as the recruitment of the
leukocyte-specific non-receptor Tyr kinase LCK to the TCR complex. Coreceptors
CD4 and CD8 have different capacity to recruit LCK to the TCR, thus directing
lineage decision [ 203 ]. In addition, differentiation into the CD8

+ lineage requires

93 In peripheral T cells, store-operated Ca 2 + entry through plasmalemmal Orai proteins is the main
route for Ca 2 + entry.
94 Channel Na V 1.5 is not expressed in mature CD4

+

T cells.