[Mechanism of inhibitory effect of intravenous immunoglobulin on neonatal umbilical cord blood lymphocytes].
OBJECTIVE
The expression of CD25, CD45RA, CD45RO on umbilical cord blood mononuclear cells (CBMCs) and CD3(+) T lymphocytes was investigated to explore the mechanism of immunosuppressive effects of intravenous immunoglobulin on neonatal immune function.


METHODS
Umbilical cord blood mononuclear cells and CD3(+) T lymphocytes isolated from 8 neonates were studied. The expression of CD25, CD45RA, CD45RO on umbilical cord blood mononuclear cells (CBMCs) and CD3(+) T lymphocytes induced with various stimuli of different combinations of IVIG and phytohemagglutinin (PHA) including (1) control group, (2) PHA activation group, (3) IVIG pre-inhibition group, (4) PHA pre-activation group, (5) PHA+IVIG group was measured with four-color immunofluorescence antibodies staining-flow cytometric technique. The results were also compared with peripheral blood mononuclear cells of 8 adults (PBMCs).


RESULTS
IVIG inhibited the PHA-induced proliferation of CBMCs as reflected by the decreased expression of CD25 and CD45RO. The amounts of CD25(+) and CD4(+)CD45RO(+) CBMCs reached 77.52% +/- 2.31% and 64.29% +/- 3.09% after PHA use. But a decreased response in CD25(+) (7.66% +/- 1.20% and 7.78% +/- 1.46%) and CD4(+)CD45RO(+) CBMC (3.18% +/- 1.90% and 3.11% +/- 0.08%) was observed when IVIG was added in both IVIG pre-inhibition group and PHA+IVIG group. As compared with PBMCs, IVIG failed to induce the increase of the expression of CD45RA in CBMCs whereas CD45RA(+) PBMCs increased from 54.93% +/- 3.63% to 72.77% +/- 0.39% in IVIG pre-inhibition group. Moreover, IVIG inhibited the expression of CD25 and CD45RO on cord blood CD3(+) T lymphocytes no matter whether they were activated with PHA or not. The amounts of CD25(+) and CD4(+)CD45RO(+) CD3(+) T lymphocytes reached 97.92% +/- 2.19% and 80.41% +/- 5.57% after PHA use. But a decreased response in CD25(+) CBMCs (77.29% +/- 0.63%, 51.48% +/- 1.85% and 62.73% +/- 1.24%) and CD4(+)CD45RO(+) CD3(+) T lymphocytes (35.47% +/- 2.55%, 40.14% +/- 1.16% and 36.41% +/- 2.96%) was observed when IVIG was added in IVIG pre-inhibition group, PHA pre-activation group and PHA+IVIG group, and the degree of inhibition of IVIG on cord blood CD3(+) T lymphocytes was much lower than that of CBMCs.


CONCLUSIONS
Cord blood T lymphocytes activation was inhibited by IVIG through the inhibition of CD25(+) CBMCs expression and the prevention of transformation from CD4(+)CD45RA(+) cells into CD4(+)CD45RO(+) cells. This IVIG-mediated suppression of activation in cord blood T cells may be derived from the indirect effect of other immune cells or molecules other than the direct effects on T cells. IVIG failed to induce the increase of expression of CD45RA in CBMCs, which may be related to the fact that majority of CBMCs were CD45RA(+) cells, but this may not rule out that the immunosuppressive effect of IVIG could be accomplished by the increase of CD45RA(+) cells in adult peripheral blood mononuclear cells. The suppressive effect of IVIG on CD4(+)CD45RO(+) T lymphocytes may account for its inhibitory effect on immunoglobulin production of neonates' B cells. Considering that naïve CD45RA(+) cells dominate in neonates and IVIG can inhibit transformation from CD4(+)CD45RA(+) cells into CD4(+)CD45RO(+) cells, it is recommended that IVIG should be used properly in neonates, otherwise it may deteriorate their poor immune function especially when it is used for prophylaxis or as a treatment of neonatal non-infectious diseases, and its immunosuppressive action will increase the susceptibility of neonates to infection.
Hao
Yi-qun
YQ
Immunology/Oncology Department, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Second Medical University, Shanghai 200092, China.
Chen
Tong-xin
TX
Zhu
Ya-zhong
YZ
Li
Qing-sheng
QS
D000328:Adult; D017252:CD3 Complex / Q000096:biosynthesis / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D007155:Immunologic Factors / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D007231:Infant, Newborn; D007275:Injections, Intravenous; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008297:Male
D017252:CD3 Complex; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D017493:Leukocyte Common Antigens