T-Lymphocytes - Chronic Obstructive Pulmonary Disease - page 222

per mm3 (7,84). The increase of CD8 þ T-cells in the peripheral blood might
be a reflection of the increase in the T-cells in the lung, that might ''spill
over'' (107) or more likely to increase transit of the activated T-cells toward
the lung. If that were the case patients with more cells in the lung would also
have more cells in the peripheral blood.
The inconsistency in the finding of CD8 þ increases in peripheral blood
should not be surprising. These cells are usually expressed as percentages of
total T-cells or CD4 þ = CD8 þ ratios; as CD4 þ T-cells, especially in patients
with severe COPD, are also increased in the lung, they should follow the
same path as CD8 þ and also spill over or be found in transit in the periph-
eral blood. In favor of this possibility are the findings of Majori et al. (110).
They reported that there was no difference between the percentage of T-cells
in the peripheral blood in patients with COPD and controls. However, the
percentage of CD4 þ T-cells expressing intracellular IFN-g was significantly
higher in the COPD group, while the percentage of CD4 þ T-cells expressing
intracellular IL-4 was significantly lower. These findings indicate that the
CD4 þ T-cells in smokers, expressing IFN-g are activated, and consequently
increased in numbers in the lung and could spill over or, more likely, are in
transit in the peripheral blood. This increase in the CD4 þ T-cells in the per-
ipheral blood, together with increases in CD8 þ , will keep the CD4 þ = CD8 þ
ratio unchanged.
It would be important to know if the CD4 þ and CD8 þ T-cells in the
peripheral blood are just cells ''in transit,'' homing to the lung, or activated
T-cells with a ''systemic mission'' and capable of producing disease beyond
the lung. The possible association of any of these findings with the develop-
ment of the systemic manifestations in COPD would be an important field
for investigation (111).
In contrast to the findings in active smokers, de Jong et al. (108)—and
later Hodge et al. (112)—reported that ex-smokers with COPD clearly have
an increase in CD8 þ T-cells and decrease in CD4 þ = CD8 þ ratio, while
active smokers with COPD were no different than the controls. The excess
CD8 þ cells might represent a population of memory effector cells able to
circulate in the peripheral blood. The number of central memory and mem-
ory effector cells is proportional to the number of effector cells generated
after antigen presentation by DCs and as the number of CD8 þ effectors
are orders of magnitude larger than CD4 þ , it would not be surprising that
CD8 þ effector memory cells outnumber CD4 þ in the peripheral blood. In
favor of this interpretation are the findings of Hodge et al. (l12). These
authors showed an increased propensity of peripheral blood T-cells
(CD4 þ and CD8 þ ) in COPD to undergo apoptosis, most likely due to
increased Fas, TNF-a, and TNF-R1 expression by these T-cells, an event
most likely related to the state of activation of these cells, as the study of
Majori et al. (110) above also showed.