Table 4. Potential effects of SHS/direct CS on effector lymphocyte function against TB.

Lymphocyte subtype	Effects of SHS/direct CS
TH1 cells	Reduced number of TH1 cells and decreased production of IFNγ per cell (128,129)(H,H). Potential mechanisms include CS-derived reactive oxygen species-induced necrosis of T cells (130)(H), T cell exhaustion as CS increases PD-L1 on antigen presenting cells, leading to engagement of programmed death (PD-1) receptors on T cells (58,91,92,131)(H,H,H,M/H), downregulation of CD28, and upregulation of CTLA-4 (132)(M). In adolescents exposed to SHS, the percentages of blood memory CD4+ and CD3+ T cells (CD45RO+) were inversely related to the degree of SHS exposure although there was a direct relationship between the percentages of naïve CD3+ and CD4+ T cells (CD45RA+) and degree of SHS exposure (133)(H). In contrast, T cells from both CS-exposed mice and human smokers fluxed calcium, proliferated and produced IFNγ at levels comparable to T cells from control mice and non-smokers (134)(M/H).
TH2 cells	Increased influx of IL-4-positive TH2 cells in the lungs (39)(M).
TH17 cells	In mice, CS increased TH17 cells but only after relatively long-term exposure (135)(M). The percentage of TH17 cells is increased in the blood of healthy cigarette smokers (136)(H) and CS exposure of human lung explants increased IL-17 expression (137)(H).
CD8+ cells	Smokers have increased CD8+ cells in their airways than non-smokers (138)(H). CS increased the proliferation and inhibited the apoptosis of CD8+ T effector cells but increased both the proliferation and apoptosis of CD8+ Tregs (139)(H). CS exposure of mice increased CD8+ (and CD4+) T cells (140)(M).
MAIT cells	Human subjects exposed to CS had reduced circulating levels of CD26hiCD161hi MAIT cells (141)(H).
B cells	Chronic smoking is known to cause a polyclonal B cell lymphocytosis (142)(H). In adolescents exposed to SHS, there was no difference in the percentages of blood B lymphocytes and the degree of SHS exposure (133)(H). B cells from CS-exposed mice and human smokers fluxed calcium, proliferated and produced immunoglobulins at levels comparable to control mice and non-smokers (134)(M/H). In contrast, others have shown that CS-exposed or nicotine-exposed rodents have reduced number of B cells as well as reduced calcium flux and decreased proliferative capacity in response to antigenic stimulation although the amount of experimental CS exposure in these studies were greater than that typically seen in human smokers (143,144)(M,M).

M, murine; H, human; M/H, murine and human.