Effects of influenza immunization on humoral and cellular alloreactivity in humans.
BACKGROUND
Alloreactive T cells and anti-human leukocyte antigen antibodies mediate transplant injury. Environmental exposures, including vaccinations, may activate the alloimmune repertoire leading to accelerated allograft injury. To test whether vaccination impacts human alloimmunity, we analyzed humoral and cellular immune reactivity in subjects undergoing influenza vaccination.


METHODS
We serially obtained blood samples from 30 healthy subjects and 8 kidney and 9 lung transplant recipients who received influenza vaccination, and from 20 healthy unvaccinated controls. We measured cellular and humoral anti-influenza responses, anti-human leukocyte antigen antibodies, and alloreactive T-cell immunity (interferon-gamma ELISPOT) at 0, 2, 4, and 12 weeks after vaccination.


RESULTS
Vaccination induced influenza-reactive humoral and cellular responses in control subjects and in transplant recipients. Only two of 30 vaccinated volunteers developed new alloantibodies, but none of the transplant patients. Vaccination also specifically and significantly augmented cellular alloimmunity based on reactivity to a panel of stimulators in both healthy subjects and in transplant recipients within 4 weeks of vaccination. The enhanced cellular alloresponse waned toward prevaccine levels by week 12.


CONCLUSIONS
Our findings newly demonstrate that influenza vaccination can have a significant impact on the potency of the alloimmune repertoire. Because the strength of the alloresponse influences long-term graft function, our results suggest that further investigation of alloimmune monitoring after vaccination is needed.
Danziger-Isakov
Lara
L
Department of Pediatrics, Cleveland Clinic, Cleveland, OH, USA.
Cherkassky
Leonid
L
Siegel
Hanni
H
McManamon
Mary
M
Kramer
Kristen
K
Budev
Marie
M
Sawinski
Deirdre
D
Augustine
Joshua J
JJ
Hricik
Donald E
DE
Fairchild
Robert
R
Heeger
Peter S
PS
Poggio
Emilio D
ED
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization / Q000009:adverse effects; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology*; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D013997:Time Factors
D000914:Antibodies, Viral; D006680:HLA Antigens; D007252:Influenza Vaccines; D007518:Isoantibodies; D007371:Interferon-gamma